A Single Drug Solution for Treatment, Prevention of HIV?


Scientists seek to create powerful defense system that will both attack the virus and prevent infection.

Scientists seek to create powerful defense system that will both attack the virus and prevent infection.

Researchers are inching closer to the creation of a single drug that could not only attack HIV, but also prevent it.

In a study published this month in in Nature Communications, scientists are seeking to create a drug that could prevent HIV infection, treat patients already infected with HIV, and wipe out all dormant copies of the virus in patients with more advanced disease. Investigators at the Salk Institute for Biological Studies moved closer to the creation of a treatment that customizes a defense system utilized by many bacteria and alters the scissor-like machinery to recognize the virus.

"Evolution has led to some of the most astonishing mechanisms for protecting organisms against their natural pathogens," senior author Juan Carlos Izpisua Belmonte said in a press release. "Understanding the immune responses by which bacteria protect themselves against viral infections has allowed us to engineer novel platforms for the targeting of devastating viruses, such as HIV, in human patients."

After a copy of the HIV virus enters a human cell, it utilizes the cell's molecular machinery to manufacture copies of the genetic material of the virus and buries the copies into the cell’s genes. The host cell subsequently makes new copies of the virus that spreads throughout the body.

Current HIV drugs attack the individual steps of the viral lifecycle, as some treatments halt the virus from integrating into cell DNA, while others attempt to stop the affected cells from producing more copies of the virus, the study noted.

These drugs do not, however, remove copies of the virus hidden within the cellular DNA, which can reactivate after remaining dormant for a long period of time.

"Patients normally need drugs every day or every week for their whole lives, because of the HIV that can be latent," first author Hsin-Kai Liao said. "This costs money, time, and effort."

To solve this issue, prior research tabbed the CRISPR molecular defense system used by bacteria to slice foreign DNA at specified spots to edit genes. For the current study, investigators hypothesized that CRISPR may be programmed to destroy viruses inside human cells.

When CRISPR was added to guide RNAs and other molecules used by the system to treat immune cells infected with HIV, and it was found that CRISPR successfully cut the correct areas in HIV genes, which deactivated the virus. This process completely removed the virus from nearly 72% of cells.

Additionally, CRISPR cut loose copies of HIV that initially infected the cell and sliced copies of the virus that were dormant within the DNA of the cell.

"CRISPR can actually excise the virus out of the human genome," Liao said.

The researchers also added the CRISPR system to human cells before HIV infection, which sliced up copies of the virus before it could begin replication.

"The main advantage of this technology is not only that viral DNA integrated into the human genome can be eliminated, but perhaps, most importantly, the prophylactic application," Belmonte said. "By eliminating the virus at the early steps of its life cycle, we can altogether prevent the infection of human cells in an analogous manner to how conventional vaccines work."

Further research will be necessary to evaluate how the system could be used to treat human patients and how quickly HIV will evolve to escape CRISPR.

The researchers will next examine the effectiveness of adding more guiding RNAs to the CRISPR system so the defense can simultaneously recognize more areas of the virus.

"The HIV virus can mutate very quickly," Liao said. "If we target multiple regions at the same time, we reduce the chance that the virus can develop resistance."

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