Preclinical evaluation of AAV9-coSMN1 gene therapy for spinal muscular atrophy: efficacy and safety in mouse models and non-human primates.

ABSTRACT:

Background

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by the loss of motor neurons in the spinal cord. Our team has initiated clinical trials using adeno-associated virus serotype 9 (AAV9) vectors carrying a codon-optimized human SMN1 (coSMN1) gene, delivered via intrathecal (IT) injection. Here, we present the preclinical research that laid the groundwork for these trials, offering comprehensive data on the efficacy and safety of AAV9-coSMN1 in both murine models and non-human primates.

Material and method

We developed a codon-optimized hSMN1 expression cassette and analyzed SMN protein levels using Western blot and immunofluorescence. Taiwanese SMA-like mouse model was employed to assess tail length preservation, as well as to examine motor neu

SUBMITTER: Ma W 

PROVIDER: S-EPMC12042585 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature