854. Optimization of AAV Serotype and Promoter for Increased Distribution of Expression in Both Somatic and Central Nervous Systems of Mice

Fu, Huiling; Muenzer, Joseph; Lu, Kang; Jennings, Jerillyn S.; Samulski, R. Jude; McCarty, Douglas M.

doi:10.1016/j.ymthe.2005.07.397

Cited by 2 publications

(1 citation statement)

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“…When designing the payload of an rAAV vector, a promoter should be selected that can best ensure transgene expression in the target tissue or cell type of interest. Whereas early studies often made use of the broadly expressing cytomegalovirus (CMV) promoter for efficient transgene expression [162], this promoter is notoriously subject to transcriptional silencing [163]. A popular alternative is the hybrid CMV/chicken beta actin (CBA) promoter, also known by the alternative acronym CAG.…”

Section: Payloads Of Raav Vectorsmentioning

confidence: 99%

Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases

Li,

Vasan,

Kartono

et al. 2023

Biomedicines

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Recombinant adeno-associated virus (rAAV) vectors are gene therapy delivery tools that offer a promising platform for the treatment of neurodegenerative diseases. Keeping up with developments in this fast-moving area of research is a challenge. This review was thus written with the intention to introduce this field of study to those who are new to it and direct others who are struggling to stay abreast of the literature towards notable recent studies. In ten sections, we briefly highlight early milestones within this field and its first clinical success stories. We showcase current clinical trials, which focus on gene replacement, gene augmentation, or gene suppression strategies. Next, we discuss ongoing efforts to improve the tropism of rAAV vectors for brain applications and introduce pre-clinical research directed toward harnessing rAAV vectors for gene editing applications. Subsequently, we present common genetic elements coded by the single-stranded DNA of rAAV vectors, their so-called payloads. Our focus is on recent advances that are bound to increase treatment efficacies. As needed, we included studies outside the neurodegenerative disease field that showcased improved pre-clinical designs of all-in-one rAAV vectors for gene editing applications. Finally, we discuss risks associated with off-target effects and inadvertent immunogenicity that these technologies harbor as well as the mitigation strategies available to date to make their application safer.

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Section: Payloads Of Raav Vectorsmentioning

confidence: 99%

Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases

Li,

Vasan,

Kartono

et al. 2023

Biomedicines

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In search of proof‐of‐concept: gene therapy for glycogen storage disease type Ia

Koeberl

2012

J of Inher Metab Disea

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The emergence of life threatening long-term complications in glycogen storage disease type Ia (GSD-Ia) has emphasized the need for new therapies, such as gene therapy, which could achieve biochemical correction of glucose-6-phosphatase deficiency and reverse clinical involvement. We have developed gene therapy with a novel adeno-associated virus (AAV) vector that: 1) prevented mortality and corrected glycogen storage in the liver, 2) corrected hypoglycemia during fasting, and 3) achieved efficacy with a low number of vector particles in G6Pase-deficient mice and dogs. However, the gradual loss of transgene expression from episomal AAV vector genomes eventually necessitated the administration of a different pseudotype of the AAV vector to sustain dogs with GSD-Ia. Further preclinical development of AAV vector-mediated gene therapy is therefore warranted in GSD-Ia.

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854. Optimization of AAV Serotype and Promoter for Increased Distribution of Expression in Both Somatic and Central Nervous Systems of Mice

Cited by 2 publications

References 0 publications

Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases

Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases

In search of proof‐of‐concept: gene therapy for glycogen storage disease type Ia

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