October 04, 2013
Biodistribution of AAV8 vectors expressing human LDL receptor in a mouse model of homozygous familial hypercholesterolemia
This study was performed to support a proposed clinical trial to evaluate AAV8 gene therapy for familial hypercholesterolemia (FH). It describes the biodistribution data following intravenous delivery of AAV8 in the mouse model of FH.
October 04, 2013
Combined rod and cone transduction by AAV2/8
This study demonstrates that AAV8 transduces the cones of the pig retina as well as AAV9. Efficacy was dependent on the promoter selected. Subsequently, AAV8 was shown to restore cone function in the mouse model of Leber congenital amaurosis type 1 (LCA1), confirming the utility of AAV8 in gene therapy of diseases affecting both rods and cones.
September 11, 2013
Therapeutic AAV9-mediated Suppression of Mutant SOD1 Slows Disease Progression and Extends Survival in Models of Inherited ALS
The mouse model of amyotrophic lateral sclerosis (ALS), like the human disease, has proven very difficult to treat. In this study, AAV9 was used to deliver an shRNA to reduce superoxide dismutase 1 (SOD1) gene expression in the mutant SOD1G93A mouse. This not only increased survival when delivered at birth, it also significantly slowed disease progression after disease onset in the mouse model. This suggests that the therapeutic may be beneficial in the familial forms of ALS that are caused by SOD1 mutations, and may also be beneficial in some patients with sporadic disease.
August 22, 2013
Systemic Delivery of MeCP2 Rescues Behavioral and Cellular Deficits in Female Mouse Models of Rett Syndrome
This article demonstrates the utility of AAV9 in treating the female mouse model of Rett syndrome. Previous publications had used male mice; however, this neurologic disease primarily affects females. Gene replacement by systemic administration of AAV9-MeCP2 in affected female mice stabilized or reversed symptoms.
August 06, 2013
Enhancing the Utility of AAV Gene Transfer Through Inducible Tissue-Specific Expression.
Regulatable promoter systems, such as the rapamycin-inducible ARGENT system, can be incorporated into gene therapy products in order to regulate the timing and level of transgene expression. This paper demonstrates that the ARGENT promoter can be further refined to be tissue-specific. AAV9 was used to deliver the ARGENT system in vivo, demonstrating liver-specific or heart-specific gene expression that was stable, regulatable, and reproducible over multiple cycles of induction.
July 10, 2013
Capsid Serotype and Timing of Injection Determines AAV Transduction in the Neonatal Mice Brain
Six different serotypes of AAV were injected intracerebroventricularly (ICV) into neonatal mice, on postnatal days P0, P2, and P3. Of the serotypes tested, AAV8 and AAV9 showed the most widespread transduction.
May 30, 2013
Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza
The authors used AAV9 to deliver a broadly neutralizing anti-influenza monoclonal antibody to influenza’s portal of entry, namely, the nose. They demonstrated complete protection of mice and ferrets from several different isolates of influenza that have been associated with human pandemics. This strategy has the potential to be rapidly deployed to protect against emerging pandemics as well as seasonal influenza.
July 10, 2013
Transduction of the Central Nervous System Following Intra-cerebroventricular Injection of Adeno-associated Viral Vectors in Neonatal and Juvenile Mice
This paper shows AAV9 distribution throughout the brain after ICV injection into slightly older mice (5 and 21 days of age). There was widespread transduction throughout the brain, but with different patterns of cell-specific gene expression, depending on the time of injection and the promoter used.