Scientists Use CRISPR to Block HIV Replication Inside Living Cells

Modern medicine has made incredible progress in the treatment of HIV. Years ago, infection with HIV would almost certainly lead to developing AIDS, but treatment can now keep the disease at bay. Even with daily antiretroviral therapy (ART), the pathogen continues to hide in a patient’s cells. Researchers from Japan’s Kobe University say they’ve successfully used the CRISPR/Cas9 gene editing platform to block the replication of HIV in living cells.

Around 35 million people around the world are infected with HIV, but many of them keep their viral levels low with ART. Medications cannot currently root out all signs of HIV infection because of the way the virus reproduces. HIV is a retrovirus, meaning it’s an RNA-based virus when it infects cells. However, the first thing it does upon entering a cell is use an enzyme called reverse transcriptase to transform into DNA and hide in the cell’s genome. When the cell produces its own proteins, it also ends up making new viral particles.

Even if you eliminate all the circulating HIV in the body, there’s still the virus hiding inside cells. That’s why the Japanese team looked at CRISPR/Cas9. This technology is based on a bacterial antiviral system, but scientists have learned how to use it to precisely snip DNA in living cells. The team used CRISPR to alter HIV’s genome while it was still hiding inside cells, thus limiting its virulence.

The experiment targeted two of HIV’s nine genes that are key to the proliferation of the virus. The genes in question are known as tat and rev. Without those genes, HIV doesn’t work. Researchers used genetic information from six common HIV subtypes to build guide RNA (gRNA) that pointed the Cas9 protein at the right DNA segments. They introduced it into cells using a modified lentiviral vector.

CRISPR was not used to add new genes or make any specific substitutions. The point was simply to damage these critical HIV genes. With the mutated and non-functional genes, the virus was crippled. According to the team, their method of targeting multiple HIV gene variants was successful in limiting viral proliferation. Almost no functional virus particles were produced by the cells.

This experiment happened in a cell culture, but future study could result in a method for doing the same in humans. If you can reduce circulating viruses to zero and nuke viral genomes inside cells, you may finally be able to cure HIV.

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