A gene-editing attack technique called CRISPR/Cas9 may need to be reworked as experts found that HIV can resist it. In a new study, the method was able to stop viral replication, but it also resulted in unanticipated resistance.
CRISPR (clustered regularly interspaced short palindromic repeats) is a natural defensive mechanism of the body, which involves having spurts of odd-patterned configuration in between DNA that matches that of some viruses. This means CRISPR carries pieces of dangerous viruses that attacked earlier on, so that the next time they attempt to harm, the body will recognize them and defend accordingly.
Cas9 (CRISPR-associated proteins) is a group of enzymes that efficiently cuts DNA and rips apart invading viruses. The genes that encode for Cas are situated near CRISPR patterns, making their combination a promising process for viral death.
Many experts were delighted when they found out about the CRISPR/Cas9 mechanism. Some even looked at its feasibility to fight off human immunodeficiency virus (HIV), which has crippled a large number of people all over the world. The recent study was able to yield good results initially, with viruses being killed by the approach. However, HIV seemed not to go down without a fight because those that escaped the CRISPR/Cas9 therapy came out even stronger.
The Mechanism Of HIV And How Experts Plan To Use Gene-Editing For Counterattack
HIV is so clever that it targets the immune system at once. The virus specifically invades immune system cells called T cells, which are the core of adaptive immunity. HIV infects by inserting its genome to the DNA of the host cell and manipulating its machinery to create more copies of the virus.
One approach to counter this is to equip the T cells with gene-editing abilities so they can identify and destroy HIV when it occurs. That's where the use of the CRISPR/Cas9 mechanism comes in.
The Big Surprise
The researchers did use CRISPR/Cas9 to HIV in an experiment. At first, they were able to cripple the virus, but that success appeared to be short-lived. After two weeks, the team observed that the T cells started releasing copies of the virus that had survived the CRISPR/Cas9 attack. Turns out the virus has created mutations near areas where Cas9 had been programmed to slice.
Senior study author Chen Liang from McGill University in Canada describes some of the mutations as tiny, however they were able to alter the sequence, leaving Cas9 unable to recognize it.
"Such mutations do no harm to the virus, so these resistant viruses can still replicate," says Liang.
Staying Positive
The results of the study should serve as a guide, maybe a caution, for those who are looking to use CRISPR/Cas9 as part of an antiviral therapy.
Liang does not think that the situation is hopeless, but he believes there are some techniques that can be done to overcome the letdown. For example, experts may try to target multiple sites with the CRISPR/Cas9 therapy or use other enzymes apart from Cas9.
Liang says CRISPR/Cas9 provides new hope that one day a cure may surface not only for HIV, but also for many other viruses as well. He acknowledges that the journey toward the goal is still long. There may be barricades and limitations that need to be solved, but they are confident they will be successful.
The study was published in the journal Cell Reports on April 7.
