Benitec in AIDS collaboration with LA's City of Hope

Brisbane gene-silencing company Benitec (ASX:BLT) and renowned Los Angeles medical research centre City of Hope (COH) have joined forces to develop a genetic bear trap for the AIDS virus, that they hope will prolong the lives of AIDS patients.

City of Hope AIDS researcher Dr John Rossi has devised a multi-pronged strategy around Benitec’s proprietary gene-silencing technology that he hopes will lock the virus out of patients’ cells, and block its replication.

Rossi, chair of the division of molecular biology with City of Hope’s Beckman, will use a lentivirus cousin of the AIDS virus to insert a protective package of genes into patients’ own bone marrow cells ex vivo.

Rossi said the package of ‘silencer’ genes, based on Benitec’s double-stranded RNA-interference (ddRNAi) technolology, will target highly conserved sequences shared by the virus’ tat and rev genes, that he believes should be common to the many different strains of HIV circulating in populations around the world.

The package will also silence the human CCR-5 gene, which codes for an accessory receptor on the surface of CD4+ lymphocytes and macrophages.

The virus requires both receptors to be expressed on the surface of the lymphocyte to invade. Individuals carrying a mutation that deletes the CCR-5 receptor are naturally resistant to HIV, but otherwise healthy, so unlike the CDC4 receptor, CCR-5 appears non-essential to immune-system function.

In theory, HIV patients who undergo the City of Hope therapy should become resistant to the virus, while the other the ‘silencer’ genes targeting tat and rev provide backup, by disrupting the virus’s replication in already-infected lymphocytes and macrophages.

Rossi said the lack of a small-animal model of AIDS has impeded pre-clinical testing, but the COH hopes to take the potentially life-saving therapy into a phase 1 trial in human volunteers in the second half of 2005.

The volunteers will be chosen from patients with AIDS-related lymphoma, who already require a bone-marrow transplant. Grafting patients with their own, modified stem cells will avoid rejection problems.

The Benitec-COH system should also avoid the current problems of drug resistance associated with extended use of today’s anti-HIV drugs. Because the patient’s own stem cells, once installed in bone marrow, replicate indefinitely, the new therapy could effectively provide a lifetime cure.

Dr Larry Couture, director of the Centre for Biomedicine and Genetics at COH, said the agreement with Benitec reflected “a new approach to cooperative public-private technology development for translational medicine.

“This is [our] first collaboration of this nature in which City of Hope, as a preferred partner in drug and biologic development, offers unprecedented pre-clinical research, biologics manufacturing and clinical study expertise to biopharmaceutical partners such as Benitec,” he said.