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to Section One | to Arts & Entertainment
posted Friday, February 26, 2016 - Volume 44 Issue 09
Enzyme 'scissors' can cut HIV out of DNA sequence, study says
Section One
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Enzyme 'scissors' can cut HIV out of DNA sequence, study says

by Mike Andrew - SGN Staff Writer

A laboratory-engineered enzyme can cut HIV out of patients' DNA sequences, a new study says.

The research by German scientists, published in Nature Biotechnology, may show how to cure HIV infections.

Currently, HIV patients can suppress the virus using antiretroviral drugs, but HIV continues to subsist in the patients' DNA even when it is no longer detectable in their blood. The drugs are also expensive and may cause side effects and drug resistance.

The German scientists, however, have developed a customized enzyme that is able to identify what are called HIV 'proviruses' - HIV genomes that implant themselves in human DNA. The enzyme then 'snips' the HIV genome out, like 'scissors.'

The enzyme, called Brec1 (for broad range recombinase 1), reliably sliced HIV sequences from a number of cell types: bacteria, human cell lines used in research, cells collected from patients with HIV infections, and those of 'humanized' mice with HIV.

Though the strategy is very early in its development - nowhere near the clinical trial stage - the data so far point to an effective and safe way to help drug treatments completely finish off HIV infections.

This is a 'promising strategy for future clinical applications,' the study's authors say.

Brec1 originally sought out and snipped a completely different genetic sequence, the study says, but researchers coaxed it into chopping HIV by making mutated versions.

Then, researchers screened the mutants for the ability to cut sequences related to the latent HIV sequence. They then repeated the process, gradually shifting the target sequence until it matched HIV.

With each cycle, the researchers would look for a mutated version of the enzyme that got closer and closer to cutting the specific genome of the HIV provirus. After 145 cycles, they had produced a version of Brec1 that cut the exact provirus sequence and only that exact sequence.

Once Brec1 slashes the flanking HIV sequence, the whole provirus gets extracted and destroyed. Then the enzyme patches up the DNA break it created.

In lab tests, researchers found that Brec1 could cut the HIV sequence out of every cell type they tested. The enzyme also carved out HIV without any toxic or genetic side effects, the researchers noted.

So far, the research has focused on 'humanized' mice, animals modified to carry human immune cells that can be infected with HIV.

Given a dose of Brec1 delivered via a genetically engineered virus, HIV infection in the mice declined over time to the point where HIV was no longer detectable, even though uninfected human cells persisted in the animals.

If the result holds up in humans, the enzyme may finally offer a solution to lingering HIV infections in patients on drug treatments.

'Complete elimination of replication-competent HIV, including latent viral reservoirs, may be the only way to achieve a genuine cure,' the authors conclude.

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