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.

Others have had the idea to use Nobel Prize winning siRNA technology to block this gene but the team led by Professor Ramesh Akkina is the first to report complete gene suppression.

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."

However, drugs don't completely block their therapeutic target and so using siRNA could prove to be a more powerful approach. However, not every HIV/AIDS drug target will be amenable to this technique. Their high specificity, touted as their big advantage over traditional drugs, could also prove to be their downfall because mutations in the virus would then stop the siRNA from working.

CCR5 is less likely to suffer from this problem since it is a human cellular target, rather than part of the virus. However, Prof. Akkina explained that genetic polymorphism

and allelic variations do exist in the CCR5 gene, and so it was important to develop several siRNAs that all target different areas of the gene.

In order to identify pieces of RNA that would block the gene, Prof. Akkina 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 Prof. Akkina to conclude that: "overt cellular toxicity/cell death may not be an issue with these constructs".

He 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.

Prof. Akkina is currently working on this problem, using siRNAs to target both viral genes and other human genes, such as fusin (CXCR4), another viral entry route.