Gene therapy could protect against HIV infection using siRNA technology

According to a report in the journal Gene Therapy, scientists from Colorado State University, have found several small-interfering RNA (siRNA) strands that target different regions of the gene that produces chemokine (C-C motif) receptor 5 (CCR5), and totally prevent it from functioning.

For years, CCR5 has been a popular target for HIV/AIDS drug developers as it is the virus' predominant entry route into white blood cells. Attacking this target is a new strategy in drug research, as other drugs concentrate on fighting the virus itself, once it is inside the cells. Indeed, a subgroup of the human population that have a defective CCR5 gene are physiologically normal but are known to be resistant to HIV infection and disease progression.

There are currently no marketed drugs that target CCR5, although Pfizer's Selzentry (maraviroc) is on the verge of being approved by regulators for use in the US and exerts its effect through blocking this very protein.

The US Food and Drug Administration (FDA) recently issued an 'approvable letter' to Pfizer, with the world's largest pharma firm currently working to "address outstanding questions and finalise the product labelling as soon as possible."

In order to identify pieces of RNA that would block the gene, researchers used the Smart-selection design algorithm from Dharmacon, which is part of Thermo Fisher Scientific. Of the initial five tested (19 nucleotides long), three were over 90 per cent effective at blocking CCR5. Longer versions of these were then developed, which increased the efficacy to up to 98 per cent.

Four of the six also appeared to show no cytotoxic effects even at high concentrations, and the fact that all six work well at low concentrations led researchers to conclude that: "overt cellular toxicity/cell death may not be an issue with these constructs".

They also pointed out that using CCR5 siRNAs alone would not be enough to provide an adequate gene therapy as they wouldn't protect against some strains of the virus, and may even promote those strains to spread. Therefore, other genes must also be attacked by the same therapy if it is to protect fully against HIV/AIDS.