A report published in the Journal of Virology by researchers in the Netherlands states that gene editing with CRISPR Cas9 may lead to unwanted "clipping" and mutation of the sequence that the HIV virus integrates into the gene. This may activate host genes, which in turn contribute to the development of cancer, raising concerns about this potential HIV** strategy.
Gene editing technology promises to revolutionize modern medicine as well as the methods of many diseases. There are currently several potential HIV** strategies, including gene editing, which is thought to be able to permanently remove the virus from most or all body cells. Another possibility is to introduce new or modified genes inside our cells that make them resistant to viruses. However, there are risks associated with any intervention that involves our genes.
Some viral diseases and most hereditary diseases are ideal candidates for gene editing because they have a clear genetic link. For HIV, simply removing permanently integrated viral genetic material from our own genes seems to be the easy way to achieve long-lasting**. But because editing takes place in the genome of our genetic material as a whole, even minor inaccuracies can lead to undesirable health outcomes, such as the possibility of causing cancer in the future. This is one of the reasons why gene-editing interventions need to be tested in long-term safety trials for up to 15 years.
Modern gene editing technology
modern gene editing technology
Gene editing, which is widely available, has been a dream for nearly a century since the discovery of genetic material (DNA). However, most of the previous methods were very laborious and imprecise. The discovery of bacterial mechanisms has greatly advanced the development of modern gene editing. The so-called CRISPR Cas9 complexes extracted from bacteria have proven to be orders of magnitude more precise than any previous method. In short, this "machine" works by taking a piece of genetic sequence (template) from an attacking virus and then tracking its counterpart in the bacteria's own genome. When it finds the corresponding sequence, it excises the fragments in it, causing damage and dysfunction of the entire anchored viral genome.
The machine can track foreign genetic material within the bacteria's own genes because the DNA exists as a double strand (imagine two intertwined bands) and the "letter" sequence of one "band" perfectly complements the other. So, if we cut a piece from one strip, our cells can correctly regenerate the missing sequence of letters from another strip. When a template matches a sequence within a bacterial genome, CRISPR Cas9 knows it needs to be removed. By giving the editing complex different templates, we can have it cut or even insert any type of DNA sequence, which gives us the ability to remove viruses, insert protective genes, or correct damaged genes, among other things.
Another way to insert genes into cells is to modify the virus, removing its pathogenic part and using its "shell" to help certain gene products enter our cells, which is known as the gene delivery "viral vector" method.
Research
research
Microbiologists in the Netherlands have tested in the lab using different types of HIV-infected cells to verify that the gene-editing machines are accurate enough to target only the HIV provirus sequences in human DNA, and that the cleavage is precise enough to damage the DNA sequences near the cells.
They found that the editing mechanism was able to pinpoint the target (protoviral sequence), but the cleavage resulted in the random deletion or addition of DNA sequences in non-viral regions around the proviral sequence. This will have a direct impact on human DNA that receives gene editing**. Through additional laboratory methods, they also identified the ** of these unwanted DNA changes. It turns out that it is not the "editing machine" that directly changes and destroys these neighboring DNA sequences, but the DNA repair process of the cell itself.
The editing mechanism creates nicks in both strands of the DNA molecule to introduce the damaged sequence into the target (proviral sequence). Double-strand breaks are one of the strongest warning signs of danger in cells, and cells have multiple mechanisms to quickly correct breaks and connect the ends of double-stranded DNA molecules. Some mechanisms are very effective and allow for a complete and very accurate fix, while others can affect the accuracy of the fix.
In this case, the cells used a less efficient method of DNA repair. This seems to be one of the reasons for the addition or deletion of these incorrect sequences.
We have genes in our DNA that can cause or promote cancer (proto-oncogenes). Because HIV is randomly distributed in our genes, proviruses may be present next to proto-oncogenes. Usually these proto-oncogenes are "silenced" so they don't do anything;However, if the process of adding or deleting the DNA sequence as described above occurs next to the proto-oncogene when performing gene **, it may be activated. This is one of the concerns highlighted by the researchers in **, which could be a direct or indirect consequence of gene editing.
Potential and risks of gene editing
the potential and risks of gene editing
There are currently dozens of trials using genetically *** for multiple diseases, including the ongoing Phase II HIV**Excision Biotherpeutics trial. The trial used the exact same gene-editing technology as described in this article. Gene technology companies in the U.S. are also working on first-stage genes for HIV. However, in these cases, they use viral vectors to make immune cells resistant to the virus. They took a relatively small amount of cells, modified them with a vector, cultured them, and sent them back into the body. Therefore, it can be considered less risky because they do not use CRISPR Cas9 for gene editing, and they also only work on a limited number of cells in vitro.
So far, there have been some major breakthroughs, such as "bubble boy" disease, an inherited immunodeficiency disorder that often causes death in infancy, and trials that use gene editing to fight muscular dystrophy and even cancer. So, the potential is very real, but what about the risks?
There is always a trade-off between risks and benefits for any type of medical intervention;Of course, there is no such thing as a risk-free intervention. In some cases, such as advanced cancer or a genetic disorder such as bubble boy disease, the benefits may greatly outweigh the associated risks. However, for a disease like HIV, most people can live a relatively normal life after receiving **, but the balance of risks and benefits is different.
Conclusion
conclusion
The use of CRISPR Cas9 for gene editing is relatively new, and its efficacy and risks have not been fully explored. The results of this study suggest that the editing mechanism is able to find the target precisely, but the edited DNA repair process appears to be inefficient. This can lead to mutations in our DNA that can increase the risk of disease, especially cancer later in life.
However, we must keep in mind that these findings are from in vitro cell cultures and may not provide a complete picture of what is actually happening. To some extent, these effects may be more pronounced in actual biological systems, where there are hundreds of thousands of times more cells in our body, so the likelihood of error is higher. However, throughout the system, cells often behave differently than lab dishes, so their DNA repair may be more efficient. In addition, some viral infections, including HIV, are known to increase the risk of cancer in their own right, so the risk of cancer may be even greater if HIV is not obtained**.
Genetics is a very broad field with more and more patterns, methods, and techniques emerging. Although this article only touches on the latest findings of CRISPR Cas9, it does not generalize the risks to other approaches. In any case, more research is needed to clarify all these issues before any conclusions can be drawn.