http://regenxbio.com/business_development/recent_research/ en john.sutter@sutter-group.com Copyright 2013 2013-05-09T15:32:21+00:00 Using engineered AAV capsids with an ovalbumin immunodominant peptide, this study demonstrates that AAV2 capsid stimulates a T-cell response in mice, but that AAV8 does not. This is despite equivalent levels and kinetics of capsid antigen presentation. These data do not support a previously proposed hypothesis from a hemophilia B clinical trial that CTLs to AAV capsid clear transduced cells.

]]> 2013-05-09T15:32:21+00:00 Treatment of neurologic diseases with novel AAV serotypes has been gaining momentum, as these vectors have been shown to transduce much of the CNS with less invasive routes of administration. This study demonstrates that Intrathecal delivery of AAV9 as well as AAV7  in non-human primates gives widespread gene expression in the CNS and the peripheral nervous system.

]]> 2013-03-27T20:03:50+00:00 This study in non-human primates demonstrates the abilities of AAV8 and AAV9 to transduce cones as well as rods in the retina. Because the NHP retina is the most similar to humans, it suggests that different AAV serotypes could be used for different retinal degenerations in humans, depending on which cells of the retina need to be most efficiently transduced.

]]> 2013-03-27T20:00:42+00:00 The authors show that AAV9 delivery to the CNS by injection into the CSF (including intrathecal injections) is not inhibited by the presence of serum neutralizing antibodies (NAbs) to AAV9, up to titers of at least 1:128. This suggests that for diseases that might be treated through this route of administration, the vast majority of patients would be eligible for treatment, given the low frequency of high titer NAbs to AAV9.

]]> 2013-01-15T13:37:55+00:00 A mouse model of familial hypercholesterolemia (LDL receptor-deficiency) was created that has a lipoprotein phenotype that much more closely resembles that of humans than previous mouse models. In this model, gene therapy with AAV8 encoding the human LDL receptor significantly corrected the high plasma cholesterol levels at doses of vector that are able to be developed for human use. In addition, the vector had beneficial effects in treating the more common heterozygous FH phenotype.

]]> 2012-11-14T15:25:54+00:00 The authors compare intravenous and intracoronary delivery of AAV5, AAV6, and AAV9. Optimal vector/delivery was determined by quantitating both the percentage of cells positive for GFP expression and GFP intensity. AAV9 was found to be superior in both methods of delivery, with IV delivery resulting in more homogeneous but low-level cardiac expression, and IC delivery resulting in more intense but less homogenous cardiac expression.

]]> 2012-09-25T10:31:58+00:00 The authors demonstrated the superiority of AAVrh.10 as compared to AAV5 for the treatment of metachromatic leukodystrophy in the mouse model. The efficacy shown supports a proposed clinical trial, which is expected to begin dosing patients shortly. In this month's issue of Human Gene Therapy researchers discuss the signficance of this study.

]]> 2012-08-28T14:01:28+00:00