BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Embryo

Can CRISPR Gene Editing Cause Problems in the Embryos it is Meant to Customize?

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On March 25, 2022

In Student Post

Researchers from around the Tri-State area came together in 2020 to examine the effectiveness of the Crispr-Cas9 double stranded DNA break (DSB) induction on human embryos to repair a chromosomal mutation. The study, which was published in Cell, began with sperm from a mutated male patient at the EYS locus, which causes retinitis pigmentosa blindness. The researchers then attempted to use CRISPR-Cas9 technology to repair the blindness gene in a number of fertilized embryonic stem cells that carried the EYS mutation.  The results showed that about half of the breaks in the experiment went unrepaired, which resulted in an undetectable paternal allele. After mitosis, the loss of one or both the chromosomal arms was also common. This study shows that using CRISPR-Cas9 technology is still in its early days, and needs to be further vetted before it is used to treat patients.

CRISPR Cas9 technology

Instead of correctly and consistently editing the genome of the embryos, the Crispr-Cas9 wreaked havoc, leaving behind chromosomal trauma. The data shows that the embryos started to tear apart and get rid of big pieces of the chromosome that had the EYS mutation, some losing the entire chromosome. The promise of Crispr technology is about changing one gene, but how can that be done when a larger, untargeted part of the genome is also being altered? Dr. Egli, the paper’s main author, brought up a more likely use for the Crispr editing: deploying it as a form of “moleculure bomb”, sent in to shred unwanted chromosomes. An important part of using gene editing is the ability to consistently predict the outcome, However, the resulting “mosaicism prevents inferring the genotype of the fetus from a biopsy and is thus incompatible for clinical use”, according to the Cell authors.

There were many rarities that appeared in the alleles of the embryos used. With a small sample size, due to the difficulty to acquire human embryos, there was no ability to rule out rare events. Although there were combinations of maternal and paternal alleles that showed interhomolog events, they occurred after the two-cell-stage injections, all mosaic. A single Cas9-induced break can result in outcomes in the human embryo that suggest species-specific differences in repair. In on-target sequencing of the cells, the detection of only a wild-type maternal allele might have been because of the unrepaired breaks and the loss of the chromosomal arm or the loss of the entire chromosome. This study shines light on the dangers of Crispr gene editing. The quotes from researchers, doctors, and genealogists all echo the same risk, we must walk before we can run. Testing and ensuring the safety of using Crispr on an embryo before the first round of DNA replication happens is crucial to the ultimate promise of gene repair. If it can’t be done safely with no off target effects, then Crispr “would be deeply unethical”, according to Dr Faraheny from Duke University.

CRISPR: A Possible Solution to Genetic Diseases?

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On March 20, 2022

In Student Post

A few decades ago in science fiction, there were talks of things like genetic modification in babies. This was more along the lines of creating the ‘perfect’ human, rather than using genetic modification to stop certain genetic illnesses. An example of this is in the 1997 movie, Gattaca, where we see an unmodified (genetically) person struggle to live in a world of genetically modified people. While it is fiction, it showed how being able to alter someone’s genetic flaws can go a long way. Despite, at the time, this seeming to just be science fiction, some of these concepts of gene alteration might become reality. These concepts becoming reality would all be due  to CRISPR.

CRISPR logo

Some of you might be thinking, “what is CRISPR?,” and that’s okay because before researching it I was thinking the same thing. CRISPR is a type of genetic engineering technique in molecular biology. This technique allows for the modification of genomes in a living organism. This technique is actually based off of CRISPR-Cas9 antiviral defense system, which can cut genomes. This has inspired CRISPR to contain Cas9 nuclease complexed with gRNA. This is the sent into a cell and is able to cut a cell’s genome at a certain position. This allows for specific genomes to be removed, as well as allowing new ones to be added. So in summary, CRISPR is a method of removing certain genomes of a cell, and in some cases replacing and/or adding a genome as well.

A genome alignment of eight Yersinia isolates

Different Alignments of Genomes

Now that CRISPR has been explained and we know what it is as well as how it works, we are now able to look at studies involving it. While CRISPR seems great and all, Heidi Ledford posted an article about how the use of CRISPR in embryos can cause some unwanted changes to the embryo. While experimenting, researches found that the use of CRISPR on an embryo can not only cause unwanted changes at the genome target site, but it can also cause changes near the genome target site. While some of you may think that the pros out-weigh the cons in this instance, geneticist Gaétan Burgio states that, “the on-target effects are more important and would be much more difficult to eliminate.” The on-target effects (negative) are so bad that it may not be worth doing even if it is to eliminate genetic diseases.  The idea that the cons outweigh stopping a genetic disease shocked me, as in our biology class we talked about genes and genetic diseases, and how even though they can be extremely rare, they can be irreversible, life changing, and in some cases fatal. This rejects the idea that the pros could out-weigh the cons, which puts a pin in this genetic modification breakthrough.

Da Vinci Studies of Embryos Luc Viatour

 Da Vinci’s Studies of Embryos

After looking at CRISPR as well as the research shown on genetic modification of embryos, I have realized how far we still are from elimination of genetic diseases. Despite issues arising in the experiment, I hope that they can put CRISPR to good work in order to stop the seemingly impermeable genetic diseases. And who knows, if we can master genetic modification with CRISPR, the ideas presented in Gattaca could soon seem like reality.

 

 

Is Junk DNA Really Junk?

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On October 27, 2021

In Student Post

DNA is the base code of all living creatures. It is in every plant, animal, and single-cell organism, yet  50% of human DNA is seen to be irrelevant to bodily function. While some DNA is responsible for synthesizing materials within cells, much of it is in essence, spare genes, or ancient viruses that have become part of the human genome over time. Moreover, it has been debated whether the 50% of DNA that is not seen to be relevant is truly essential for survival. That is, can humans live without unused genetic code, or is it vital to the survival of the species?

Ácido desoxirribonucleico (DNA)

One specific element of junk DNA is transposons. Transposons are sequences of DNA that have the ability to mutate a cell or change its function as a whole. A study was conducted at the University of California, Berkley, and Washington University on transposons, as written in the So-called Junk DNA – Genetic “Dark Matter” – Is Actually Critical to Survival in Mammals, by the University of California, Berkley. The studies looked at a specific transposon in mice called MT2B2, one that controlled the growth rate of cells in a fertilized embryo, and when the embryo would implant in the uterus of the mother by initiating the short gene Cdk2ap1. When the researchers disabled the MT2B2 transposon using CRISPR-EZ, the mice created a longer version of the gene Cdk2ap2. This new version of the gene decreased cell growth and increased the period of implantation. The teams found that half of the baby mice died before birth without this transposon in their DNA. When the transposon was disabled, the mice sort randomly instead of uniformly in the uterus, and some may cause the death of a developed fetus and or the mother.

The team at Washington University researched the transposons turned on before embryos are impacted into the uterus in humans, rhesus monkeys, marmosets, mice, goats, cows, pigs, and opossums. The team used scRNA-seq, which records messenger RNA levels to indicate which genes are being used. With this technique,  the team saw that in every animal, a group of species-specific transposons was turned on. While the transposons were different for each species, the result of their use was nearly the same for all eight cases. Moreover, the gene Cdk2ap1 was expressed by all eight animals, but the amount of short and long versions of the gene expressed was unique for each one. While an animal that needs fast implantation uses more of the short version of the gene, like the mouse, animals with little to none of the shorter version of Cdk2ap1 took two weeks to longer for implantation to occur, like the cow.

Baby Mouse Rehabber

For these transposons to be promoting the expression of the Cdk2ap1 gene, at a certain point in history, a virus entered the organism and eventually part in a mutually beneficial symbiotic relationship with the organism until it evolved into the current iteration of the transposon. When viruses blend into the DNA of a species, they can be used to regulate and perform tasks that the cell could not previously perform. This can create a wide range of evolutionary options in species. Additionally, the main difference between the different genomes of species is the regulation of genes. By studying transposons, scientists can better understand differences in the genome of one species to another. With the understanding of this transposon, scientists could now begin searching further into junk DNA, as the removal of the transposon studies by the two universities proved lethal 50% of the time. Moreover, undiagnosed patients could have junk DNA mutations that lead to health problems, but those cases are currently a mystery to the medical world. Transposons are just the beginning of scientists dive into junk DNA, and who knows what wonders they will find next?

Embryo Gene Editing can Ensure Offspring Do Not Inherit a Deafness Gene!

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On January 23, 2020

In Student Post

Denis Rebrikov, A scientist in Russia has done research regarding ways in which he can edit the genome sequence of an embryo in order to prevent the fetus from developing certain gene mutations, specifically in this case a hearing problem or possible complete deafness. His plans are very controversial to some, who believe the possible risks of very harmful mutations to DNA that would be passed onto direct and future offspring, outweigh the possible benefits. However, some people find this scientific possibility to be worth the risk, if it means not passing a potentially very harmful gene down to offspring. If these methods are done correctly, it should alter the genome sequence in the embryo so that future offspring off that embryo will not inherit the negative mutation.

One couple shared their story in detail, in which both parties have a hearing deficiency, the man with partial deafness, and the woman completely deaf. Their biggest hope is to have children who will not inherit hearing issues, because of the apparent challenges they have had to face themselves because of them. They would be the first couple to perform this gene editing on an IVF embryo, so they obviously have some reservations. One of those being publicity, but more importantly the potential risks of using the CRISPR genome editor. They already have a daughter with hearing loss, but they never chose to test her genes for mutations, nor did they get her a cochlear implant to aid her hearing, because of the potential risks of that. When they finally tested her genes, they learned that she had the same common hearing loss mutation called 35delG in both her copies of a gene called GJB2. The parents then tested themselves, realizing they were both 35delG homozygous, meaning their daughter’s mutations were not unique to her, they had been inherited.

If either the mother or father had a normal copy of the GJB2 gene, a fertility clinic could have more easily created embryos by IVF and tested a few cells in each one to select a heterozygote–with normal hearing–to implant. At this stage, Denis Rebrikov informed them that CRISPR genome editing would be their only option. However, the process presents possibly deal breaking risks, such as mosaicism, in which a gene edit might fail to fix the deafness mutation, which could create other possible dangerous mutations like genetic disorders or cancer. The couple has not decided to go through with the editing just yet, but it is something they are open to in the future as more possible new research or test subjects become available.

Explaining the CRISPR Method: “The CRISPR-Cas9 system works similarly in the lab. Researchers create a small piece of RNA with a short “guide” sequence that attaches (binds) to a specific target sequence of DNA in a genome. The RNA also binds to the Cas9 enzyme. The modified RNA is used to recognize the DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location… Once the DNA is cut, researchers use the cell’s own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.” -US National Library of Medicine Genetics Home Reference

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Woman with a hearing aid 

If you had the opportunity to alter something in the gene’s of your baby’s embryo, would you? Under what circumstances would you consider this, and what risks might stop you from deciding to do it? Comment down below.

 

 

Forbidden Baby Editing

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On January 21, 2020

In Student Post

We all at this point in life have come to know what gene editing is. The technology for it is slowly and forever becoming more and more advanced. The scary thing about editing genes is the fact that we have to potentially affect a baby’s life their entire time alive. It has many different problems which is why its going to take a long time for it to fully get approved in the hospital.

Well unfortunately in an article found here there was a fright to figure out that someone had actually edited the genomes of some babies without people knowing. Many scientists condemned scientist He Jianku as it came to light that he had done something that the science was not ready for yet. He used CRISPR Cas9 tech in order to alter some genes of a few babies. The definition of CRISPR is here but basically it is a general tech to edit the genomes of babies that haven’t been born yet. People were up in arms about the process because he had bypassed the ethical laws and needed up editing the genes of a real live human. People in the science community go on to say that the CRISPR technology just isn’t ready to be executed on a human. There needs to be many more trials before it is used on a person for real. There is progress to make sure this doesn’t happen such as fines and bans from research however they are trying to make sure that it doesn’t happen at all. It gives scientists a bad name and he is trying his best to not let that happen. Technology will always advance and the hard part is trying to make sure that tech is ethical. Hopefully this gives insight to how we can prevent things like this happening in this day and age

Genetically Modified Babies?

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On January 21, 2020

In Student Post

A decade or two ago, the idea of being able to modify embryos was straight out of a science-fiction movie. However, last November, Chinese scientist He Jiankui genetically modified twin girls’ embryos to have resistance to the HIV virus using a process called CRISPR. His actions have sparked a global panic, as many people feel that current regulations are not enough to keep the scientific community’s actions ethical.

To understand this issue, it is important to understand its individual components. CRISPR is a gene-editing tool that was discovered in 2007 and became widely used in 2013. Essentially, a scientist decides what portion of DNA they would like to alter, and transcribes the sequence into RNA. This RNA finds the portion of DNA with the specific code and then the Cas9 enzyme “cuts” the DNA, allowing a new sequence of DNA to take its place.

The image depicts functions of CRISPR Cas9 technology.

Dr. He used CRISPR Cas9 technology to try to block the HIV pathways in twin girls while they were still embryos. As this experiment was recent, the long-term effects of it are unclear. In addition, as these girls were not developed at the time of their gene editing, they did not give consent to have a treatment that could be detrimental to their health. Furthermore, looking at the Centers for Disease Control website, HIV is primarily acquired by the use of unsafe needles to inject drugs and sexual contact. Using clean needles and condoms can greatly decrease one’s risk of getting HIV, and if a HIV-positive person takes suppression medicines, the viral content of HIV in their blood can become undetectable. Dr. He’s actions gave the twin girls undue risk, with little possible benefit.

In the future, this method of gene editing may be used to prevent or treat genetic diseases, but people have little knowledge of the long-term implications of using this technology on embryos. At the moment, the lack of global legislation regarding this gene-editing technology leaves a lot to be wondered about the future of this tool. According to Victor Dzau who works in the United States National Academy of Medicine, “The silver lining is that the world was awakened by the conduct of Dr. He, and we are all working very, very hard with all good intentions to make sure that this doesn’t happen again—not in the fashion that He did it. And that someday, if and when the technology is ready—and I think all of us are very bullish about this technology—that it will be helping humankind in the right way, knowing the risks and knowing the benefits.” After Dr. He’s experiment, many are in favor of halting the use of CRISPR on human embryos for at least five more years, so more research can be done on the subject. However, legislation, which the world has seen little of, holds a stronger weight than mere recommendations. In Russia, Denis Rebrikov is planning to create CRISPR babies, and regulations in the country regarding his specific goals remain unclear. How will CRISPR embryo editing evolve in the coming decades? Will CRISPR gene editing be as common someday as IVF is today?

 

A Much-So-Symmetrical Embryo

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On October 14, 2018

In Student Post

Developmental biology has taken a step further in understanding the connection made between the placenta and fetus by testing a hypothesis that involved slowing down the growth of one limb on an animal. Scientist Alberto Roselló-Díez used laboratory raised mice to test out his hypothesis by genetically manipulating the cells of a fetus in a petri dish. He then inserted the genetically modified cells into the mouse’s back left leg. A deeper look at Díez’s work explains that he uses a “p21” suppressor which is also known as an “antiproliferative”. In doing so, Roselló-Díez is suppressing chondrocyte cells (found in cartilage) from forming, thus preventing the mouses bones from lengthening.

In response to the cellular suppression, the nature of the fetus’s growth as a whole slows down to the growth rate of the left hind leg;  putting me in the mind of the phrase- “no man left behind”. This is described to be a “compensatory mechanism”, in which the entire fetus makes up for the compromised development of the mouse to keep it’s symmetry.

You might be wondering- “how does the placenta play into this?” Apparently, the cells of the placenta systemically communicate to the tissues of the other limbs, and warn them to “SLOW DOWN!” Therefore the fetus of the mouse relies on biological signals from the mother’s placenta.

Picture by Maneesha S. Inamdar

All in all, minimizing the growth rate of limbs is intriguing because it leaves me wondering the extent of the experimental purpose. Will it be that in the future we will use the p21 suppressor on human fetuses? Will this study lead to a breakthrough for unanswered cosmetic and orthopedic phonomena? These questions are yet to be undertaken by developmental biologists and maybe even doctors.

GATTACA is Here!

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On March 17, 2018

In Student Post

            In August of 2017 Scientists finally had figured out how to successfully edited genes in human embryos in order to treat serious disease-causing mutation using advanced CRISPER/Cas9. This is a  major milestone as it brings scientists closer to the reality of being able to genetically engineer babies in order to re

File:CRISPR-Cas9-biologist.jpg

Photo by J Levin W

pair faulty genes. This concept has always been feared due to the lack of success and safety of previous genetic tests, however, this study proves that scientists can now successfully edit genes.“We’ve always said in the past gene editing shouldn’t be done, mostly because it couldn’t be done safely,” said Richard Hynes, a cancer researcher at the MassachusettsInstitute of Technology who co-led the committee. “That’s still true, but now it looks like it’s going to be done safely soon,” he said, adding that the research is “a big breakthrough.” Genetic testing has also been regarded as unethical due to the possibility of eugenics, in which wealthy families would pay to have their embryos adjusted to get enhanced cosmetic traits such as height and muscle mass. “What our report said was, once the technical hurdles are cleared, then there will be societal issues that have to be considered and discussions that are going to have to happen. Now’s the time.” This successful study has come out only months after a national scientific committee recommended new guidelines for modifying embryos in which they strongly urge gene editing be used solely for severe hereditary medical conditions.

Stem Cells…Key to Youth and Controversy

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On December 4, 2015

In Student Post

Have you ever wondered what it would be like to be young forever? With the help of stem cells, this is possible. Stem cells can regenerate skin tissues and can also be used to treat diseases. However, something as enticing as living forever has its controversies. There are two types of stem cells: embryonic (ES) and adult (iPS); the embryonic stem cells are the controversial type.

Embryonic Stem Cell

Embryonic Stem Cell

The only way to effectively use the embryonic stem cell is to kill a four to six day old embryo. Some people view this act as killing a baby, which sparks ethical arguments about whether or not to utilize embryonic stem cells. To avoid this controversy, scientists have been trying to use stem cells from iPS cells instead of ES cells, but they questioned the power of iPS cells compared to the ES ones.

Because genes may differ in the iPS cells from the its source, the ES cells, there is a possibility that these two cells do not have the same capability. One scientist notes that the source of iPS and ES cells differ, which can lead to differences in gene activity. The ES cells are derived from embryos, which are not completely identical to iPS adult cells.  However, recent scientific research shows that these two types of stem cells have more equal capabilities than scientists’ initially thought.

Scientists conducted an experiment to compare the genetic makeup between the ES and iPS cell. They manipulated the male type of each cell, which eventually allowed the ES cell to transform into the iPS cell. They concluded that the iPS cells genetically matched the ES cells’ parents, and that the iPS cells had more similarities with the ES cells than iPS cells had to each other.

Even though these two experimental cells genetically matched, the two cells were not identical. The experiment showed 49 genes that differed between the two stem cells. Because of this difference, scientists needed to see if this affected the functional capability of the cells. The researchers conducted another experiment that analyzed 2 of the 49 genes. One helps take in glucose, while the other helps break it down. Even though these two genes were more active in the ES cell than the iPS cell, they were equally efficient at their respective jobs. The scientists concluded that these two specific cells were functionally equivalent.

The many experiments that have been conducted on the topic of stem cells contribute to the increase in research for more ways to utilize stem cells, without the ethical controversy. Scientists are starting to employ different technological devices, such as 3-D printers to help develop and build stem cells. This ability to fabricate cells using technology overcomes previous obstacles of limited stem cell resources.

– Source Article

– More fun facts about stem cells here

Monkey Be, Monkey Do

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On January 10, 2012

In Student Post

Are you one of those people who has always wondered about scientist’s progress in creating genetically amalgamated Monkeys? Well, if the answer is yes, then you need wonder no more, because Scientists have recently created their very own combinations of primate genes known as Chimeric Monkeys through the extensive study of stem cells and embryonic tissue.

The term Chimeric Monkey, stemming from the Greek Chimera, essentially describes the scientists efforts of combining various monkey genes in a prospective embryo, and empregnating a mother with said genes to direct what the eventual monkey child will develop into based on its new genes. It should be noted also that experiments with chimeric mice have also been a great asset in this venture, as they have provided certain genes which serve as “knock out” genes for  ones that the scientists wish to delete when creating the new monkey genome.

Shoukhrat Mitalipov of the Oregon National Primate Research Center at Oregon Health & Science University has been one of the primary figures in researching this new breakthrough chimeric studies saying that “The possibilities for science are enormous.” The basic procedure for creating the Chimeric monkeys entails the initial mixing of embryonic cells very early in their development that are classified as totipotent, or still having the capability of creating an entire animal with placenta, and other life sustaining tissues. Mitalipov has stated that “The cells never fuse, but they stay together and work together to form tissues and organs”.

So what do you all think? Is this all really a huge breakthrough in genetic science, or perhaps going a bit too far in what we were meant to manipulate?

Oh, and by the way, Mitalipov emphasized that there is no need or plans for chimeric humans,  just in case you were wondering

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