The complete suppression of the gene CCR5 in white blood cells leads to a stronger protection against HIV, suggests a study published online this week in Gene Therapy. The results were achieved using multiple new generation small interfering RNA molecules (siRNAs), which target several regions of the CCR5 gene and have the potential to add significantly to the present arsenal of anti-HIV drugs.
The CCR5 co-receptor is essential for the entry of HIV into cells but is dispensable for normal cellular functions and therefore an ideal therapeutic target - 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. In the present study, Ramesh Akkina and Joseph Anderson derived several highly potent siRNAs capable of complete suppression of CCR5 expression. When these siRNAs were introduced into transgenic white blood cells produced from cultured stem cells and challenged with a predominantly transmitted R5-tropic strain of HIV-1, remarkable resistance to viral infection was observed. This suggests these anti-CCR5 siRNAs are among the most effective demonstrated to date and are very promising candidates for clinical applications.
According to the authors, "For innovative AIDS therapies to succeed in the long term, novel strategies need to be employed. In this regard, gene therapy approaches that focus on cellular molecules involved in viral attachment have great potential". They propose that the use of CCR5 siRNAs, in combination with siRNAs directed against T cell tropic viruses and delivered via a single gene transfer vector to modify blood cells, might confer broad anti-viral protection against HIV.
Ramesh Akkina (Colorado State University, Fort Collins, CO, USA)
(C) Gene Therapy press release.
Message posted by: Trevor M. D'Souza
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