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Intravenous Injections in Neonatal Mice
Published on: November 11, 2014
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Systemic gene therapy using an AAV44.9 vector rescues a neonatal lethal mouse model of propionic acidemia
Randy J Chandler1, Giovanni Di Pasquale2, Eun-Young Choi1
1National Human Genome Research Institute, Bethesda, MD 20892, USA.
Molecular Therapy. Methods & Clinical Development
|September 25, 2023
Summary
Gene therapy using AAV44.9 vectors shows promise for propionic acidemia (PA). A single newborn dose improved survival and reduced toxic metabolites in a new PA mouse model, highlighting potential for metabolic disorder treatments.
Area of Science:
- Biochemistry
- Genetics
- Gene Therapy
Background:
- Propionic acidemia (PA) is a rare, severe metabolic disorder.
- Current treatments for PA are insufficient, necessitating novel therapeutic approaches like gene therapy.
Purpose of the Study:
- To evaluate the efficacy of AAV44.9 vectors for delivering a therapeutic PCCA transgene.
- To establish and utilize a new genome-edited mouse model for studying PA.
Main Methods:
- Generated a Pcca-/- mouse model using genome editing.
- Administered AAV44.9 PCCA vectors systemically to newborn Pcca-/- mice.
- Assessed survival rates, plasma methylcitrate levels, and transgene expression in liver and heart.
Main Results:
- AAV44.9 PCCA vector administration at 1e11 vg/pup increased survival in Pcca-/- mice.
- Treated mice showed reduced plasma methylcitrate levels.
- High PCCA transgene expression was observed in the liver and heart of treated mice.
Conclusions:
- AAV44.9 vectors demonstrate therapeutic potential for propionic acidemia.
- The Pcca-/- mouse model accurately recapitulates PA phenotypes.
- AAV44.9 vectors may be suitable for treating various metabolic disorders requiring hepato-cardiac gene delivery.
Keywords:
AAV44.9PCCAcardiac tropismgenome editingmouse modelneonatal gene therapyorganic acidemiapropionic acidemiapropionylcoa carboxylase deficiencysystemic gene therapy
