Researchers use CRISPR gene-editing to target HIV, might create resistance

Credit: Weyland Brain Nutrition via Flickr Creative Commons Credit: Weyland Brain Nutrition via Flickr Creative Commons

A team of eight scientists from Guangzhou Medical University recently published a paper that outlines their study on genetic modification of human embryos. The team used a recently developed gene-editing tool called CRISPR CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) to study a specific section of the human genome that could be used to make humans resistant to HIV.

CRISPRs are actually DNA sequences in prokaryotic cells (e.g. bacterial cells) that help protect these cells from invading viruses. These sequences are representative of the virus’s own genetic material.

When a virus attacks, these CRISPR undergo transcription (copying DNA into RNA), and the resultant RNA acts as a “guided missile.” It identifies the target genetic sequence in the virus that matches the RNA and allows cell machinery to destroy it. By destroying that part of the virus’s genome, this process stops the virus from replicating and functioning in its usual manner, thereby preventing infection.

This artificial method of gene-editing involves the production of specific RNA sequences in a laboratory that are aimed for a specific gene (or characteristic) in the target animal’s genome. This RNA is then used to guide cell machinery to that location, which then works to either silence the gene (not allow that characteristic to be expressed) or edit the gene (change the characteristic).

The research study that was carried out by the team from Guangzhou Medical University involved introducing a specific mutation in the CCR5 gene called the CCR5-delta32.

The presence of CCR5-delta32, found in 20 percent of Caucasians, produces some form of immunity to HIV and hinders the progression of the disease. While this study produced only four successful embryos out of the 26 tested, the researchers noted that it provided data that would help develop a better mechanism for gene-editing and understanding why pregnancies terminate early.

In their paper, published in the Journal of Assisted Reproduction and Genetics, the research team points out several details that had a huge impact on the outcome of the experiment. First, the identification of a specific sequence in the genome that would affect a particular characteristic is hard to pinpoint, especially when it is often the result of several genes working together to produce a single characteristic. Second, this process needs to be refined to account for the effects of genetic mosaicism, which is the production of two different types of cells that influence the same characteristic of an animal.

The team also highlights the need to make the techniques more specific, so that no unwanted changes in other genes take place. In fact, this was the most common cause behind the unsuccessful embryos. The team concludes their paper by stating that although the prevention (or reduction) of several crippling diseases (e.g. Huntington’s disease) is conceptually possible through this technology, considering the ethical and biological risks in doing so, such an invasive procedure must only be performed when it’s absolutely necessary.

Given the delicate ethics of genetic testing in human embryos, this research team used human embryos that would not have developed, or would have been abnormally developed. The zygotes were 3PN, which means that they contained three pronuclei, usually from two sperms and one oocyte (egg cell) nucleus.

These zygotes can develop substantially in-vitro, but not later on, which is why they make good test subjects for gene-editing processes. In addition to that, these embryos were discarded at most after three days. In 2015, another study published by a different group from Sun Yat-sen University in Guangzhou, used CRISPR to modify the gene for thalassemia. That study was the first of its kind and sparked off an international debate on the ethics surrounding genetic experimentation with human embryos.

In December 2015, the International Summit on Human Gene Editing held at the National Academy of Sciences in Washington, D.C. concluded that while the use of CRISPR in the study of “non-viable” embryos would bring about a revolution in genetic studies, production of a human pregnancy after modification of the zygote and introduction of permanent changes in a human being’s genome would be “irresponsible” and off-limits given the current state of the technology and societal attitude towards it.

Despite their support for such experimentation under the given conditions, such research is still ineligible for federal funding.