We all hope that Calimmune's treatment for HIV will be a success but if it is not, all is not lost. Delivery has been a problem for all gene therapies, including Cal-1. Now the team at UC Davis (mentioned in previous posts) has perfected a technique for extracting purified stems cells from a soup of transfected cells, thus increasing the purification of a new treatment.
Although other HIV investigators had previously bioengineered stem cells to be resistant to HIV and conducted clinical trials in human patients, efforts were stymied by technical problems in developing a pure population of the modified cells to be transplanted into patients. During the process of genetic engineering, a significant percentage of stem cells remain unmodified, leading to poor resistance when the entire population of modified cells is transplanted into humans or animal models. In the current investigation, the UC Davis team introduced a "handle" onto the surface of the bioengineered cells so that the cells could be recognized and selected. This development achieved a population of HIV-resistant stem cells that was greater than 94 percent pure.
The team at UC Davis is led by Dr Joseph Anderson. He started his work on a treatment for HIV as part of a team that included Dr John Rossi, (City of Hope and scientific advisor to Benitec [OTCPK:BNIKF, OTCPK:BTEBY]. The team split up. Dr Rossi continued his work at the City of Hope and Dr Anderson moved to UC Davis and continued his research. As both teams had the same genesis it is not surprising that the anti-HIV strategies employed by both teams are very similar - shrna with multiple targets and a decoy.
While the team at City of Hope went on to run a clinical trial for its HIV treatment (this trial was supported by Benitec), Dr Anderson worked on perfecting the rate of transfection/transduction (the number of stem cells modified by the viral vector). His team applied for, and was granted, FDA approval to run a clinical trial but was unable to find funding at that time. The latest advancement in treatment purity will no doubt lead to funds becoming available.
The City of Hope trial confirmed that treated stem cells continued to survive and transform in the body but higher rates of initial transfection would be required if the treatment was to be efficacious. The UC Davis teams seems to have met this challenge.
While the exact transduction rate for the Calimmune trial has not been published, I would be surprised if it was as high as 30 percent. If the UC Davis team achieved a purity of 94 percent, that would be a game changer in the field of gene therapy for the treatment of HIV.
With Calimmune about to announce the completion of the dosing of its second cohort and possibly the start of cohort three, and UC Davis about to start its HIV trial, 2015 could go down as a watershed year in the genetic treatment of HIV, with ddRNAi right at the forefront.
Note: UC Davis is yet to license ddRNAi from Benitec.
Disclosure: The author is long BTEBY.
Additional disclosure: This article is not intended to be investment advice. Readers should do their own research.