BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: DNA (Page 5 of 8)

Crispr-Cas9 is the gateway to a new frontier in genetic engineering. Here’s The good and the bad.

For a number of years now, molecular biologists have been diving increasingly further into the field of genome editing. The latest development into the field is the emergence of CRISPR-Cas9. CRISPR-Cas9 has risen to prominence over other potential methods of genome editing due to its relatively simple construction and low cost. CRISPR-Cas9’s original primary and intended purpose was to help fix mutations within DNA, and with this it could theoretically help eradicate entire diseases. This application of CRISPR is wholly positive, however with the increasing prevalence of the technique other potential uses have been discovered, and some of these potential uses raise profound ethical questions.

One of the main concerns of people skeptical about CRISPR is their assertion that once the door to the wholesale genetic editing of offspring is open, there is no going back. This, on its own, is a reasonable concern. The ability to choose a child’s sex, eye color, hair color and skin complexion is very likely to be made available to by CRISPR in the coming years. CRISPR does not yet have the capability to influence more abstract elements of the genome, such as intelligence and athletic ability, but this may not be far off. There are legitimate concerns that this is a slippery slope towards a dystopian society similar to the one seen in the movie Gattaca, where society is stratified into two distinct classes: those who are genetically engineered and those who are not.

Another concern raised by some scientists is the overall safety of genetic editing. A potentially very hazardous negative result of CRISPR is the possibility of an “off target mutation.” An off target mutation is the result of CRISPR mutating something other than the intended part of the genome and it could have disastrous consequences. Now, many scientists believe that with further advancements in the field the likelihood of something like an off target mutation occurring could be reduced to almost zero. However, it is important to examine the risks of any new process, and the prospect of something like an off target mutation occurring is certainly noteworthy.

For more information click here.

What does the future hold for CRISPR-Cas9?

Genome editing, or the technologies in which scientists can change the DNA of an organism, is on the rise, especially with its latest development, CRISPR-Cas9, the most efficient method of all of the methods to edit DNA.

Like many other discoveries in science, CRISPR-Cas9 was discovered through nature. Scientists learned that certain bacteria capture snippets of DNA from invading viruses, making DNA segments called CRISPR arrays, helping them remember the virus to prepare for future invasions of that virus. When they are confronted with that virus again, RNA segments from the CRISPR arrays are created which target the DNA of the virus, causing the enzyme Cas9 to cut the virus’ DNA apart, which would destroy the virus.

 

We use the same method in genome editing with CRISPR-Cas9 by creating RNA that binds to a specific sequence in a DNA strand and the Cas9, causing the Cas9 to cut the DNA at that specific sequence. Once this is done, the scientists create a sequence to replace the one that was cut to get the desired genome.

This technology is most prominently used to attempt to treat diseases, where the somatic cells’ genomes are altered which affect tissues, as well as prevent genetic diseases where the sperm or egg’s genome is changed. However, the latter causes some serious ethical concerns of whether we should use this technology to enhance human traits. But this begs the question that if we start using it more and more to prevent genetic diseases, will this open the door for it to be used in new ways?

CRISPR Cas9, too good to be true?

After its peak in popularity following its reveal as a possible “genetic modifier” in 2013, the CRISPR Cas-9 enzyme system has been the center of debate within the biology community. Thought to be the solution to all genetic and hereditary diseases by simply “cutting out” the fault gene, new research and studies have shown that a majority of people (65 to 79 percent) have antibodies that would fight cas-9 proteins.

“The study analyzed blood for antibodies to two bacteria from which Cas9 is derived: Streptococcus pyogenes and Staphylococcus aureus. The researchers’ concern stemmed from the fact that these bacteria frequently cause infections in humans, and so antibodies to them may be in our blood” states bigthink.com

While the overall effects are unclear, the study concludes that the result would be “significant toxicity” and an unsafe use of the gene editing tool.

What do you think? Is the current risk of using Cas-9 worth the reward?

Click here, here, and here for more information.

Cas9, photo by J LEVIN W

 

Potential cure to ALS, the disease that inspired the ice bucket challenge!

You all remember the ALS ice bucket challenge, that took social media by storm, in which people dumped ice water on their heads in order to raise money and awareness to ALS, a neurodegenerative disease that progressively destroys the motor neurons and eventually leads to death.

 

There is currently no cure to this horrible disease. However new genetic technology (CRISPR) may change all that.

In short, CRISPR is a new form of gene editing that allows scientists to change an organism’s DNA.

Scientists discovered that ALS is caused by a mutation in the C9orf72 gene. ALS is often caused by a significant repeat of a segment of DNA that becomes toxic. So, using CRISPR, scientists deducted which genes either protect against or cause these toxic DNA segments. This process was extremely effective and scientists found about 200 genes that affect ALS. For example, scientists found a gene that codes for a protein called Tmx2 that when removed from mice neurons caused the mice to survive whereas not removing them killed them. This means that scientists are beginning to figure out how to cure ALS.

Discoveries such as these are revolutionary as we can now find specific causes for previously fatal, cureless diseases  such as this. In addition, using this technology we can target these specific genes and save lives.

However, whenever we discuss gene editing we must ethically consider when does this become too far? Where is the line between helping to cure people and helping to destroy society by designing babies?

To answer my own question, I think it is crucial that we take any step possible to help find cures in situations such as this. That being said, there are clear limits that must be respected. The line is definitely hazy. Let me know in the comments your thoughts about gene editing!

But for now, let’s enjoy this scientific win and hope that ALS can be officially cured. Good job ice bucket challenge for bringing attention to a serious issue that may now actually be cured.

Original Article: https://www.sciencedaily.com/releases/2018/03/180305111517.htm

Cas9: A Clue Into Making Gene Editing Safer

CRISPR is a revolutionary system that edits the DNA of living organisms with ease. The gene-editing technology offers scientists insight into genetic diseases and is widely used in biotech and agriculture, as well as to treat cancer and viral infections. But the CRISPR system and its mechanisms are not yet fully understood. However, researchers at the Ohio State University have reported that they have figured out the mechanism of how the CRISPR system figures out where and when to cut the DNA strands. This is particularly revolutionary as it provides insight into preventing gene-cutting errors.

Cas9 is an enzyme that is used by the system to target and cut out or insert specific genes. In the second of two paper published in the Journal of the American Chemical Society, the team invalidates the widely-held belief that the enzyme cuts DNA evenly. Professor of chemistry and biochemistry Zucai Suo explains that instead of cutting both sides of the DNA double-helix to the same length, Cas9  actually trims each side to uneven lengths. Ohio State doctoral student Austin Raper and his co-authors determined that the two different parts of the “Cas9 molecule communicate with each other to set the location and timing of a cut”. The first part of the molecule sets forth to cut its respective DNA strand and changes shape and signals to the second part to cut its respective second strand.

Crystal Structure of Cas9 Enzyme

Suo says that he hopes their work allows for scientists to minimize and eventually eliminate gene-editing errors. CRISPR rarely target unintended genes, but gene-editing errors can have very serious consequences. For example, if the system accidentally cut a tumor suppressor gene from a person’s DNA, they would be much more likely to develop cancer. As Raper says, it is important to understand CRISPR and the Cas9 enzyme mechanisms in order to allow CRISPR to advance to its full potential.

 

Source: https://news.osu.edu/news/2018/02/28/cas9-2cuts/

Inside Out

CRISPR is a revolutionary tool used for editing the human genome. It allows for the altering of  any given DNA sequence and ability to modify any one specific genes’ function. Its applicability consists of correcting genetic defects, treating and preventing the spread of diseases, and improving crops. However, it also raises some ethical concerns, that of which mainly is the idea that practicing CRISPR technology could be considered as playing the role of “God”.

CRISPR was adapted from the natural defense mechanisms of bacteria, which use CRISPR-derived RNA and Cas proteins, to prevent attacks by viruses and other intruding organisms. They do so by chopping up and destroying the DNA of the virus. When these components are derived and applied to more complex, organisms, it allows for the manipulation of genes.

Disregarding its ethical concerns, CRISPR can provide substantial support to a previously uncharted area of medicine; the diagnosing and treating of genetic disorders, which was previously thought to be that if one had a genetic disorder it would be incurable.  Clinical trials are set to take place both in Europe and in North America, where patients with rare genetic disorders will give cellular samples in an attempt to alter their genome, implant them back into the individual, and hopefully cure the genetic abnormality.

With CRSPR taking such progressive strides in the past year, it is not outrageous to predict what its usage could end up providing society with.  With the ability to edit the human genome there are endless possibilities in which science could evolve this area of study to benefit the human race.  CRISPR can even be used to boost the expected intelligence of an embryo.  Who knows, thirty years from now we could be watching the news and hear of the first ever “superhuman”, a genetically modified human that has been hand-coded for optimality in all human functions.

The Future of CRISPR

CRISPR is starting to become more and more of a reality as Harvard professor David Liu continues to work on it. Liu was the person who originally developed CRISPR first base editor which allowed for single letter changes in the genetic code. Liu has come up with two new features to CRISPR-Cas9.

The first is called cellular detective or CAMERA(CRISPR-mediated analog multievent recording apparatus systems). What this function does is it finds the genetic problem that is responsible for the disease someone is experiencing. Cas9 will record all the cell data and piece info together, which overall will provide more information about cancer, stem cells, aging, and overall disease.

Photo Source

The second finding is referred to as sharp scissors which is a CRISPR enzyme. Sharp scissors are way more precise and accurate than the old enzyme making is much safer. The scissors depend on specific DNA to find the region where it is supposed to cut or edit. CRISPR is progressing and as more research is being done could be used on humans in the future.

 

CRISPR used to treat diabetes, kidney disease, muscular dystrophy

Scientists have now created a new method of using CRISPR genome editing, which would allow them to activate genetics without breaking the DNA. It could potentially be a major improvement in using gene editing techniques to treat human diseases. Currently, most of the CRISPR systems work by creating DSBs or Double strand Breaks in regions of the genome targeted for editing. Many scientists and researchers have opposed creating breaks in the DNA of living humans. So the Salk group tried their new method to treat diseases such as diabetes, kidney disease, and muscular dystrophy in the mouse models.

CRISPR has proved to be a powerful tool for gene therapy, but there are still many concerns regarding some mutations generated by the DSBs though the Salk group is able to get around that concern. Originally, Cas9 enzyme couples with guide RNA to create DSBs. But just recently, researchers have used a dead form of dcas9 to stop the cutting of DNA. DCas9 would couple with transcriptional activation domains, that turn on targeted genes. But it is still difficult to be used in clinical applications.

Salk group team combined dcas9 with bunch of activator switches to uncover a combination that would work even when the proteins are not fused with one another. These components all work together to influence endogenous genes. It would influence genetic activities without having to change the DNA sequence.

In order to prove the usefulness of this method, scientists used mouse models of acute kidney disease, type 1 diabetes, and a form of muscular dystrophy. They engineered their new CRISPR system to boost the expression of an endogenous gene that would reverse the symptoms of the disease. In all three cases, they reversed disease symptoms.

To understand more, click here.

 

Photo credit: Martyn Fletcher

 

CRISPR: Back at it Again

Researchers at the Gladstone Institutes made scientific history by turning skin cells of rats into stem cells by activating a certain gene in those cells using CRISPR technology. CRISPR technology is a tool used for editing genomes through making it easy for researchers to modify gene function and easily alter DNA sequences. CRISPR stands for “clusters of regularly interspaced short palindromic repeats” and it has been a popular topic of discussion and research in the science world.

Gladstone senior investigator, Sheng Ding and his team shaped their research aiming to answer the question; “can you reprogram a cell just by unlocking a specific location of the genome?” which they answered yes at the end. They decided to test on specific stem cells that can be turned into any cell type in the body, Pluripotent cells. Ding built upon a different senior investigators discovery, Shinya Yamanaka, who found he could make stem cells out of skin cells by treating skin cells with four key proteins called transcription factors. Here Yamanaka learned that the transcription factors could change which genes are expressed in the cell, turn off genes associated with skin cells, and turn on genes associated with stem cells and he called these skin turned to stem cells Induced Pluripotent Stem Cells (iPSC).

So Sheng Ding was inspired by Yamanaka’s investigation and decided to follow the same process but treat skin cells with CRISPR  instead of transcription factors. They targeted genes Sox2 and Oct4, only expressed in stem cells, which can turn on stem cell genes and turn off those associated with different cell types. With CRISPR, Ding and his team discovered they could reprogram cells activating Sox2 or Oct4. This proved to be more efficient than previous study, as using the CRISPR technology to target a specific location on the genome immediately triggered a natural chain reaction reprogramming the entire cell into an iPSC.

This was surprising and groundbreaking for this research group as they answered their guided question but came out with more. They still want to understand how the CRISPR technology was able to trigger a change within a whole cell efficiently and immediately compared to any other tested process. This study expanded knowledge on CRISPR and its many functions, and creates more questions on why and how it can do what it does. CRISPR technology continues to confuse scientists by manipulating genes in new, different, and unpredictable ways so the next question is, what does it have up its sleeve next???

Original Article 

CRISPR, A Cure to Heart Disease?

Photo Source page: Flickr.com

     While CRISPR‘s full potential in the department of gene editing is still being researched, scientists have just successfully discovered CRISPR’s ability to correct a defective gene that causes a certain type of heart disease. Though scientists are unclear as to the type of gene corrected in order to cause this change, this discovery was made for the first time in the United States, by an experiment done on live human embryos. However the new information yielded from this experiment is extremely beneficial as it shows CRISPR’s potential in correcting genetic errors that cause disease, as well as in human embryos meant for pregnancy.

Another reason for which this study particularly stands out in its importance, is because it is much different from the other developments scientists have made in CRISPR’s abilities. Studies have been conducted worldwide using CRISPR to edit of somatic cell’s gnomes, however, this only affects individual people. This study (also done by researchers in China), has been done by editing germ line cells, which result in changes that are passed down through every following generation.

However since the changes made to cells do affect all generations that follow, scientists are unsure of the exact effects of this new technique. Although it seems that this technology will be very beneficial in stopping harmful genetic diseases, it can also be used for changing DNA to genetically determine the eye colors, height or even mental and physical abilities and intelligence. This new phenomenon is own as “designer babies”, and for many reasons, this is not something that the United States is trying to use CRISPR’s abilities for. For this reason, United States has recently created more severe guidelines regarding gene editing technology, as well as enforcing CRISPR’s use on embryos only for prevention of harmful genetic diseases, when other treatments were not successful – as a last resort – formed by the National Academies of Sciences, Engineering and Medicine.

In the study done, scientists edited out a mutant copy of MYBPC3, using CRISPR. MYBPC3 is a gene that encodes a protein that creates well maintained and structured heart muscles. Hypertrophic cardiomyopathy, known as HCM, are caused by mutations in that gene, and cause spontaneous cardiac arrest. This occurs in even the youngest and healthiest of athletes, affecting 1 in 500 humans.

In this study, the mother was carrying the normal version of a gene, while the father had the mutant gene. Using CRISPR, the scientists were able fix the mutant version, by cutting and replacing the DNA. Directly after they placed the fertilized egg in a petri dish, while introducing the genome editing parts at the same time. The results of this process proved to be very effective, as 75% of the embryos showed no mutant genome. Without the use of CRISPR when egg fertilization occurred, the chances of mutation would have been present in 50%!

From these results the researchers came to the conclusion that they have realized the potential for mosaicism. Mosaicism is when only some of the cells are edited and the rest are not affected, which results in some normal cells, as well as some mutant cells. The scientists have also gathered the effects of off-targets. Off targets are the CRISPR edited genes that appear to look like mutant genes, but are actually not. Within this study, one egg fertilized from 58 showed mosaicism, and there was no detection of effects from off-targets. Theseare very impressive results, due to the fact that both of these possible situations can cause limitations in effectiveness and safety.

Though researchers need to do over this experiment many times in order to soliditfy the effectiveness of this study for the future, if they want to use this on eggs intended for pregnancy, as the eggs fertilized in the study were not meant for pregnancy… However, the results have yielded nothing but good news for the future of CRISPR technology (besides, the risk in advancements in “designer babies”, which couldchange the future of conceiving, forever…). This article was extremely interesting for me to read, as I am very interested in studying Biology in the future, or even pursuing a track to medicine. Perhaps, I may get the chance to even experiment with CRISPR at some time in my life, as it becomes a growing presence throughout the science world!

Primary Source Article: U.S. researchershave used gene editing to combat heart disease in human embryos

CRISP New Technology: CRISPR

If you have ever seen GATTACA, and thought ‘Wow! I want to edit my genes!’… you may be in luck! CRISPR technology is a simple tool for editing ones genomes. (CRISPR is just a nickname for “CRISPR-Cas9”. ) A genome is an organism’s complete set of genes, including non-coding nucleic acid sequences. CRISPR technology has many different applications, including altering DNA sequences, modifying gene function, correcting genetic defects, and preventing the spread of diseases. Although all of these functions sound positive, CRISPR technology seems to raise ethical concerns.

 

DNA Pencil: Edit Photo By: mcmurryjulie

CRISPR stands for “clusters of regularly interspaced short palindromic repeats”, and is a specialized region of DNA with two definitive characteristics: the presence of nucleotide repeats and spacers. Nucleotides are the building blocks of DNA, and eventually proteins. CRISPR technology was adapted from the natural defensive mechanisms of bacteria. In order to repel attacks, these organisms use CRISPR derived RNA and various Cas proteins (including Cas 9), to attack foreign viruses, or other unknown bodies. CRISPRs are specialized stretches of DNA. The protein Cas9 is an enzyme that acts like a pair of “molecular scissors” which acts to cut strands of a person’s DNA. This protein usually binds to two RNA molecules: cRNA and another called tracrRNA. These two forms of RNA guide Cas9 to the target site, where it will make it’s “cut”. Cas9 cuts both strands of the DNA double helix, making what is known as a “double strand break”. This is how genes are editing.

Bouncing back to the defensive bacteria organisms that started this all, they attack foreign invaders by chopping up, and therefore destroying, the DNA. This allows for the manipulation of genes. These bacteria also use the spacers as a bank of memories which allows the bacteria to recognize viruses and other invaders.

However, due to these discoveries of how CRISPR technology works in bacteria, CRISPR technology is now going to be used to edit the genes of people to change genomes and possible diseases and phenotypes. This has caused some ethical concerns to arise in regards to CRISPR technology being used for human genome editing. Most of the changed involving genome editing are limited to somatic, or body cells, (not sperm or egg cells). Changes in body cells can’t be passed from generation to generation, but changes in sex cells can be passed onto future generations. Some of the previously mentioned ethical concerns include whether it would be a good idea to use this technology to enhance normal human traits (including height and intelligence). Due to these ethical concerns these genome edits are actually illegal in many countries!

Could CRISPR Cure Duchenne Muscular Dystrophy?

What is Duchenne Muscular Dystrophy?

https://www.flickr.com/photos/150276478@N03/34406844136

Duchenne muscular dystrophy, DMD, is an X-linked recessive disease caused by defects in the gene that makes the dystrophin protein. This particular gene is made of 79 exons, and the defects can occur on any of them. These defects lead to degeneration of skeletal and heart muscle, forcing patients to rely and wheelchairs and respirators. Without a cure, most people with the disease die by the age of 30. So, the question becomes, how can we find a cure?

What is Precision Editing?

http://www.njsta.org/news/crispr-in-the-classroom-by-simon-levien

CRISPR technology has advanced tremendously in the past several years, with each study building off the last. CRISPR technology has the capability to cut out segments of DNA, but with the risk of cutting out too much or the wrong parts. Thus, it is crucial that the cutting be as precise as possible. The CRISPR-Cas9 gene-editing tool, uses an RNA strand to guide the Cas9 enzyme along the DNA strand, skipping over important “healthy” DNA and leading the enzyme to cut a specific portion of DNA.

 How do DMD and Precision Editing Connect?

Dr. Olsen is Co-Director of the Wellstone Muscular Dystrophy Cooperative Research Center, a lab in which a team has been working to apply precision editing to DMD. The method uses one single cut of DNA along strategic points and is less intrusive than other methods. Scientists have developed guide RNAs with the purpose of finding mutation “hotspots” along the dystrophin gene. The RNA strand guides the Cas9 enzyme to 12 regions where most DMD mutations have been found. According to the article, “the new strategy can potentially correct a majority of the 3,000 types of mutations that cause DMD.” Wow! In a recent study using this method, these RNAs helped rescue cardiac function to near-normal levels in human heart muscle tissue.

Why is it Important?  

The new study demonstrates eliminating abnormal splice sites in human DNA can correct a wide range of mutation. In the case of DMD, the splice sites that were removed using CRISPR technology instruct the genetic machinery to build abnormal dystrophin molecules. Once these sites are removed, an improved dystrophin protein was observed. Even more fascinating, correcting only half of the damaged cells restored cardiac function to a healthy level. Does this sound fascinating? If you answered yes, click here to learn more!

What Does the Future Hold?

The strategy of single-cut editing may be useful for treating other single-gene diseases. News of such prospects has generated a great deal of hope for patients. Much more research is needed before CRISPRCas9 can be used on human patients. Labs and researchers around the world are working to perfect this method so that it can get federal government approval and move to the next stage – human trials. As research progresses, it will be faced with backlash from some who believe DNA should not be altered and that the technique is too risky and support from those who believe this new technique could save lives. Which side do you fall on?

Gosh…You’re Such a Caveperson!

Do you know your ancestry?  While all humans beings have their own varying histories, many are held together by one ancestral truth. They are all partly Neanderthals!  A new Neanderthal woman has been found in Croatia, and the tests being performed on her are changing the way scientists perceive human genealogy.

This discovery may be more impactful news for humans that originated outside of Africa.  For those who migrated out of Africa, scientists have cause to believe that Neanderthal DNA accounts for 1.8 to 2.6 percent of their DNA!  Considering that the common belief had been that Neanderthals accounted for 1.5 to 2.1 percent, this new knowledge is a great leap forward in understanding the way that evolution and ancestry shape the life of the modern human.  The genes that Neanderthals contributed to the modern human may affect cholesterol, mental health, body fat levels, and more.  Don’t be too alarmed about the potential negative side effects of sharing Neanderthal DNA, though.  The lead author on the study, Kay Prüfer, clarified that Neanderthal DNA is not definitively bad for your health.  He said, “We find one variant that is associated with LDL cholesterol, and the variant we got from Neanderthals is associated with lower LDL cholesterol.” So, rest assured.  Neanderthal DNA does not mean you will have certain health issues. It only means that you can.

These studies are not only teaching scientists about humans, though.  By comparing the bone fragments of the Neanderthal found in Croatia with another Neanderthal found in Siberia, scientists discovered that Neanderthals are extremely similar in DNA to one another.  Despite being from different parts of the world, both Neanderthals had strikingly close DNA structure.  This closeness in DNA is most likely a cause of a small population.  All of this information sheds a light on the low density of the Neanderthal population as well as their way of living.

While this discovery has greatly reshaped the way that we view modern human DNA, research on Neanderthals persists. Scientists hope to find even more information that will teach people about the history of Neanderthals as well as their influence on the human race.

 

How DNA damaged from radiation causes cancer

In a recent study, professors from the Wellcome Trust Sanger Institute sought to see the similarity between spontaneous cancerous tumors and cancer caused by ionized radiation. By looking at the molecular fingerprint of different types of cancers, they were able to differentiate between cancers that formed by radiation and cancers that were not formed by radiation.

In the study, they studied the mutational signatures of the DNA. Mutational signatures are just ways in which the DNA is affected by cancerous mutations. They studied the DNA mutational signatures from DNA exposed to radiation, but not necessarily cancerous, and the mutational signatures of the DNA of cancerous cells of which some were caused by radiation exposure and some were not. Both included the same signatures.

The two mutational signatures that were observed were deletion of segments of DNA bases and balanced inversion, where the DNA is cut in two places, the middle piece flips around, and the pieces are joined back in the opposite orientation from before the flip. High energy radiation is the cause for balanced inversion, since it does not happen naturally in the body. After the mutation, the DNA cannot repair itself.

This gives us a better understanding of cancer and how ionized radiation affects DNA and produces these mutational signatures. Knowing this information, this helps us recognize which tumors are caused by radiation. Once we have a better understanding of this, it will prove important for determining how each cancer should be treated. But for now, this is a strong step forward in the battle against cancer and every step of the way is crucial if we are to be victorious.

 

A Cure for Zika? Scientists successfully test a DNA-based Zika Vaccine

The Zika virus, widely known for its 2015 Latin and North America outbreak, is a mosquito-borne and transmitted virus that develops neurological complications and birth-defects in those infected. The Zika virus is able to be transmitted from a pregnant woman to her fetus, causing microcephaly– abnormal development of the brain. Currently, there exists no vaccine that would fully treat the virus, however, a solution may be in the works.

(Photo from Wikipedia Commons)

David B. Weiner, Ph.D., an executive vice president of The Wistar Institute and a developer of the Zika vaccine notes that, “Synthetic DNA vaccines are an ideal approach for emerging infectious diseases like Zika”. Synthetic DNA vaccines are vaccines with genetically engineered DNA. They work in the same way as regular vaccines, inciting cells to produce specific antigens for immunological responses. Synthetic DNA vaccines can also have potential benefits over traditional vaccines, including a higher predictability, stability, and ability to be manufactured and distributed safely and rapidly.

The current Zika vaccine in development, GLS-5700, houses multiple strains of genes with DNA instructions that tell a hosts’ cells how to react and fight off a Zika virus antigen. In late 2016, researchers tested the vaccine on 40 participants. Two groups of 20 received different does of the vaccine at zero, four, and twelve week intervals. At the end of the experiment, researchers found that all participants had developed Zika-specific antibodies and 80 percent of the participants developed neutralizing antibodies against the Zika virus.

Zika 2015-2016 Outbreak (Photo from Wikipedia Commons)

Although rare in the United States, Zika continues to threaten millions living in South and Central America. Despite being in its last stages of development, GLS-5700 and other Synthetic DNA vaccines are still prohibited from being used in the United States- although this may change with the introduction of the Zika vaccine. The future of Synthetic DNA vaccines and viral disease prevention lies in the success of the GLS-5700.

 

 

 

 

Ancient Viruses Do Good?

Photo Source

Viral DNA. Sounds like something awful, but it isn’t. One type of viral DNA called endogenous retroviruses is something that can be passed down from generation to generation.

Recently a new protein, called Hemo, in the veins of pregnant women has been discovered. This protein is believed to be made by the fetus in the placenta. But, the effect of it is unknown. The cause of this is a gene from a virus that was formed more than one hundred million years ago. In fact, human DNA consists of 100,000 pieces of viral DNA. But, it is unknown exactly what the effect of viral DNA has overall.

Some are good as they protect from disease while others are believed to cause cancer. So, is it believed that Hemo is good or bad? Well, one theory is that it is a message from the fetus to the mother that dampens the mother’s immune system so that it does not attack the fetus, which is good. But, any mutations of Hemo could be harmful or even fatal. Other viral proteins play a role in the development of a fetus. Such as how viral proteins help embryos develop tissues. Early embryos may have come to depend on tricks that viruses once used to manipulate them. Scientists are currently trying to find out more about the topic themselves

 

The journey to find a cure for cancer

What exactly does ‘epigenetic’ mean? Well epigenetic literally means “in addition to changes in genetic sequence.” The term now means any procedure to change genetic activity without changing the sequence of the actual DNA. So why is this important? Epigenetics can affect a lot of scientific research. For example DNA methylation is a hugely important epigenetic modification.

DNA methylation is where a methyl group would be added to a cytosine in a DNA sequence changing its function. This can be used in embryonic development, X-chromosome inactivation, genomic imprinting, gene suppression, carcinogenesis and chromosome stability. This means DNA methylation is very vital to growth and development- as it is a natural process- however can affect bad cells.

Examples of this are with cancer cells. DNA Methylation patterns- adding a group- are interrupted and changed when cancer is present. DNA methylation done on the promoters in tumor cells can turn off the expression of genes. In humans this can cause disruption of vital developmental pathways. This was then tested in an experiment (for now we will only observe human results because it was tested on mice as well) They tested human normal brain tissue vs. cancerous.

After testing the DNA methylation patterns on tumors, they found that 121 loci (loci is the central “hot spot” of genes) had strong methylation compared to the normal brain tissue which had 60% less. So what does all this mean??

Basically DNA methylation is a good thing in a normal environment. When cancer is present DNA methylation can change and be harmful in a negative environment such as a tumor because it causes hypermethylation.

While the take away is essentially the obvious- cancer is bad- scientists can use this data to find a correct cure for cancer and to create better medicine as some can harm even more by increasing DNA methylation in tumors. For more information on this click here.

 

 

 

How A Chemical From the Cypress Tree Could Advance Epigenetics Against Cancer

by Czechmate on Wikimedia Commons

Found in the essential oil extracted from the bark of a cypress tree, a chemical named hinokitiol shows potential to impact epigenetic tags on DNA and stop the activity of genes that assist the growth of tumors.

In order to develop an of understanding cancer, researches have had to comprehend the DNA methylation, an epigenetic function which controls gene expression. In regular DNA methylation, genes that work to fight against tumors are turned on, reducing the risk of cancer. However, if DNA methylation is negatively altered, then those cancer-fighting genes will be silenced, helping to progress cancer development. Scientists have tried to combat irregular DNA methylation and over-silencing of genes by creating epigenetic anti-cancer medications that reverse non-beneficial methylation effects. Like in most cases of medication usage, the users face unappealing side effects. Hinokitiol is attractive to scientists because it is a natural compound with many health benefits and way less side effects than modified drugs that can possibly cause mutagenesis and cytotoxicity.

 

Researchers from the Korea University College of Medicine tested the productivity of the hinokitiol chemical in a study by giving doses of it to colon cancer cells. It was found that this chemical helped to inhibit the colon cancer cells efficiency without affecting the colon cells without cancer. The scientists also found through careful inspection that the presence of hinokitiol decreases the expression of proteins DNMT1 and UHRF1; both of which are proteins that encourage carcinogenesis. In summary, the doses of hinokitiol appear to have allowed normal cells to remain healthy, while reducing the ability for the colon cancer cells to thrive and ceasing the production of proteins that promote cancer maturation.

Researchers are continuing their search for natural compounds, as opposed to artificial medications, that can prevent the flourishing of cancer in our bodies through playing a positive role in gene expression and DNA methylation.

http://www.whatisepigenetics.com/cypress-trees-epigenetically-protect-cancer/

 

 

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Sperm Epigenetics and the Next Generation

Jerome Jullien from the Welcome Trust CRUK Gurdon Institute in Cambridge experimented with frogs to see if more than just DNA is passed on to the second generation offspring.  Sperm contain something called epigenetic tags which are “chemical switches attached to the genomes of sperm.”  (It is important to understand that epigenetics does not alter an organism’s DNA.)  In order to test if these sperm epigenetics influence offspring Jullien used two types of sperm; regular frog sperm and spermatids which had different epigenetic tags.  They then injected the sperm and spermatid into genetically engineered eggs which took away some of the epigenetic tags (with specific enzymes) on the sperm.  This lead to abnormal gene expression causing problems for the offspring.

This basically shows that a male does not simply pass down his DNA to his offspring but other factors like epigenetic tags can also effect the life of their kids.  As Jullien says, “The obvious implication is that whatever experiences the father has in life that end up epigentically modifying sperm cells might also be transmitted to the offspring and affect their genetic development and characteristics.”  There is still disagreement over whether epigenetic tags on sperm influence offspring.  For example some feel the experiment tested was not realistic because the frogs were not exposed to different environments as a human would be in his lifetime.  What do you think; would epigenetic tags on male sperm have an effect on a mans offspring?

Disruption in Epigenetics Can Lead to Cancer

Epigenetics is the study of potentially inheritable gene expression that does not involve any changes to the underlying DNA sequence. Epigenetic change is natural and common, but can be brought on by changes in environment, age, lifestyle, etc. Epigenetic modifications are seen as cells terminally differentiate and end up as skin cells, brain cells, or even liver cells. Epigenetics is a constant battle between active and inactive genes. If one were to overtake the other, it would alter the equilibrium in a persons body, potentially causing cancer.

Scientists are now claiming that once they have a better understanding of epigenetics and the factors which cause the cancer, they will be able to design drugs to counter this loss of equilibrium. Recent data identified an epigenetic “writer” called methyltransferase EZH2. It’s been linked to several types of cancer including melanomas and lymphomas. They’ve also identified and epigenetic “eraser”, KDM3A, which takes on an oncogenetic role and activates tumor promoting genes in the body. Epigenomic changes also contribute to cancer’s ability to go undetected in the human immune system.

Using this information, researchers may have found the right pathway for drug targeting. Metabolites and epigenetics are tightly connected and rely on each other to stay in equilibrium. In addition, there is a strong cooperation of epigenetic factors with the transcriptional complex. Now, researchers are looking into finding a way to us this connection to suppress tumor causing epigentics, and amplify those that fight cancer.

Fabian V. Filipp, the author of the paper, states, “There is an intriguing crosstalk between metabolism and epigenetics… With both fields maturing, further synergy between epigenetic and metabolomics may deliver new therapeutic agents.”

This research is incredibly interesting because of its newness. Each day, new informatoin and research is being found in the field of epigenetics. What I would’ve liked to learn in this article is how they plan to use the metabolites to battle the cancerous cells, and in what way they would be administered. Each day we get closer to the answers. The new technology and knowledge of today may finally lead us to a cure or at least a way towards remission with certain types of cancer.

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Source article: https://www.sciencedaily.com/releases/2017/03/170324083018.htm

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