BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: anti-CRISPR

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

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.

 

 

Monkeys Cloned with CRISPR Technology

Chinese researchers used CRISPR technology to genetically edit macaque monkey embryos in order to create five monkeys with severe sleeping disorders by removing BMAL1, a gene important for circadian regulation. They then chose the monkey of the five with the most severe symptoms to clone as a model to use for future tests on monkeys with these disorders. The idea behind this research was to create a template to create clone monkeys with the disease to run tests on rather than the real monkeys themselves.

A large issue with this experiment was the ethics behind it. While the end result is to reduce the number of monkeys used in research experiments. According to the study, the disorder in the monkeys resulted in not only lack of sleep but also changes in blood hormones, increased anxiety and depression, and even “schizophrenia-like” behavior. Bioethicist Carolyn Neuhaus thinks the study is morally wrong because the monkeys are used as tools, and the research’s success is based on their suffering.

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Genes

CRISPR in the Modern World

Shawna William’s article “Crispr Babies Trial May Have Been Government Funded” on The Scientist speaks about how the most recent update on the Chinese experiment with Crispr. Scientist He Jiankui and his team came out with the new information that his experiment, which used CRISPR on the embryos of two twin girls, was funded by the government of Guangdong Province. CRISPR uses enzymes from bacteria to “edit” (aka alter) genomes of organisms to correct mutations. This technology is groundbreaking as it can be used to control the DNA of future generations. This article, in particular, focuses on the crucial point that this new information contradicts the findings of the government’s own investigation along Jiankui’s previous claims and then proceeds to evaluate all parts of this experiment.

        MIT Technology Review and the Associated Press reported in November that He modified the CCR5 gene in embryos in order to ensure that the children will be immune to HIV. One neurobiologist, Alcino Silva believes that this altering this gene has impacted the CRISPR babies and their ability to recover from strokes and better cognition, while others like geneticist Gaetan Burgio of the Australian National University believe that this study is completely wrong. Considering Burgio disputed this study over twitter instead of using a more valid outlet through publications like The Scientist, I personally do not believe that his dispute of Silva’s claim is valid. Moreover, I believe that it is extremely important that further investigation of whether the Chinese government was involved must continue. If it can be proven that the government funded this research, I truly believe that worldwide bureaucratic branches must become involved in order to reinforce that the Chinese government must uphold science ethics. Although this new tool will definitely be used to benefit the  Experiments like He’s can be detrimental to everyone involved.  

CRISPR/Cas9: Is it really the cure?

There are many benefits to the CRISPR/Cas9 defense system. But, do the pros outweigh the cons?

CRISPR is a molecule that can be programmed to target a specific sequence in a genome. It guides an enzyme, such as Cas9, to chop the code like scissors. There have been many studies and tests done using the defense. The most important advantages of CRISPR/Cas9 over other genome editing systems are its simplicity and efficiency. Since it can be applied directly in the embryo, CRISPR/Cas9 reduces the time required to change certain genes compared to other systems.

However, many attempts to use this mechanism have failed. Using the mechanism is not as easy as it sounds. A Cas9 repair is not always precise. On ZMEScience, one HIV patient tried the process. But, the HIV cells were only made stronger. Researchers equipped T-cells to hurt the virus with the enzyme Cas9. T cells are a type of lymphocyte that play a central role in cell-mediated immunity. T cells equipped with Cas9 were seen to successfully hurt the HIV genome, and make it unable to properly reproduce. This project led by Chen Liang from McGill University in Montreal, Canada seemed to work fine. But, the team noticed that two weeks later T cells were producing copies of virus particles that had escaped the CRISPR attack. The area around Cas9 only developed more mutations, aka it made the HIV stronger. It is also impossible to direct the Cas9 exactly where one wants it to go. So in essence, it is a risky gamble.

Although there are hopes for this technique to be more refined and successful in the future, for now, its uses are limited.

For more information click here.

Anti-CRISPR Proteins: What are they and can they be beneficial?

NIH Image Gallery Image Link

Understanding CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)

For many bacteria, one line of defense against viral infection is the RNA guided “immune system” known as CRISPR-Cas. This particular complex is unique because of its ability to recognize viral DNA and trigger its destruction. Scientists have used CRISPR to degrade sections of viral RNA and use the CRISPR systems to remove unwanted genes from an organism. CRISPR proteins have also been studied with the hope of eliminating serious disease and illnesses. However, this CRISPR system does not always work do to anti-CRSPR proteins that inhibit the complex from working properly.

Research 

According to an article on ScienceDaily, researchers have finally discovered how these anti-CRISPR proteins work! Research done by biologist Gabriel C. Lander from the Scripps Research Institute, discovered that anti-CRISPR proteins work by inhibiting CRISPR’s ability to identify and attack viral genomes. Just like there are different CRISPR systems, there are multiple anti-CRISPR proteins as well. One in particular mimics DNA to throw the CRISPR-guided detection machine off its course. Scientists have been able to further discover certain aspects of CRISPR and anti-CRISPR systems by using a high-resolution imaging technique called cryo-electron microscopy. They have discovered that the CRISPR surveillance complex analyzes a virus’s genetic material to see where it should attack by having proteins within the complex wrap around the CRISPR RNA, exposing specific sections of bacterial RNA. These sections of RNA then scan viral DNA, looking for genetic sequences they recognize. Lander describes these proteins as being very clever because they “have evolved to target a crucial piece of the CRISPR machinery. If bacteria were to mutate this machinery to avoid viral attacks, the CRISPR system would cease to function.” Therefore, CRISPR systems cannot avoid anti-CRISPR proteins without completely chancing the mechanism used to recognize DNA. Another type anti-CRISPR protein works a bit differently. Based on its location and negative charge, this anti-CRISPR protein acts as a DNA mimic, fooling CRISPR into binding this immobilizing protein, rather than an invading viral DNA.

Can Anti-CRISPR Proteins be beneficial?

Researchers are saying that the understanding of how these anti-CRISPR proteins work are extremely important! According to an article on GEN, the discovery and understanding of anti-CRISPR proteins actually allows researchers to have greater control over gene-edits. In this article, Dr. Sontheimer, a professor in the RNA The RNA Therapeutics Institute at UMass Medical School, expressed how “CRISPR/Cas 9 is a good thing because it introduces specific chromosome breaks that can be exploited to create genome edits, but because chromosome breakage can be hazardous, it is possible to have too much of a good thing, or to have it go on for too long.” Anti-CRISPR proteins can be beneficial and work as an off switch for CRISPR, therefore advancing gene editing!

 

 

 

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