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February 05, 2014

Gene Therapy Prolongs Survival and Restores Function in Murine and Canine Models of Myotubular Myopathy

REGENX Commentary:

X-linked myotobular myopathy is a fatal pediatric disease of skeletal muscle, for which there is no effective treatment. This paper demonstrates that intravascular administration of AAV8 encoding myotubularin prolonged survival in both mouse and dog models of the disease, providing proof of concept to support future clinical trials.

January 13, 2014

Adeno-Associated Viral Vector Serotype 5 Poorly Transduces Liver in Rat Models

REGENX Commentary:

The authors demonstrate that AAV5 is not suitable for proof-of-concept studies in rat disease models in which the liver needs to be transduced. Despite its relative efficiency in mouse and non-human primate liver, transduction of rat liver is low. In contrast, AAV8 remains suitable for liver-directed studies in rodents as well as primates.

December 29, 2013

Sustained correction of motoneuron histopathology following intramuscular delivery of AAV in Pompe mice

REGENX Commentary:

This paper describes intralingual delivery of AAV9 in Pompe mice to treat lingual dysfunction. There was robust and persistent transduction of tongue myofibers and motoneurons, and increased body weight over the course of the study.

December 29, 2013

Recombinant AAV as a Platform for Translating the Therapeutic Potential of RNA Interference

REGENX Commentary:

A review of shRNA, miRNA, and miRNA decoys and their use in therapeutic applications when expressed from recombinant AAV vectors (AAV8 and AAV9), which includes preclinical and clinical studies.

October 04, 2013

Combined rod and cone transduction by AAV2/8

REGENX Commentary:

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.

October 04, 2013

Biodistribution of AAV8 vectors expressing human LDL receptor in a mouse model of homozygous familial hypercholesterolemia

REGENX Commentary:

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.

September 11, 2013

Therapeutic AAV9-mediated Suppression of Mutant SOD1 Slows Disease Progression and Extends Survival in Models of Inherited ALS

REGENX Commentary:

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

REGENX Commentary:

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.

REGENX Commentary:

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

REGENX Commentary:

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.

July 10, 2013

Transduction of the Central Nervous System Following Intra-cerebroventricular Injection of Adeno-associated Viral Vectors in Neonatal and Juvenile Mice

REGENX Commentary:

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.

May 30, 2013

Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza

REGENX Commentary:

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.