Improved MECP2 Gene Therapy Extends the Survival of MeCP2-Null Mice without Apparent Toxicity after Intracisternal Delivery.

ABSTRACT: Intravenous administration of adeno-associated virus serotype 9 (AAV9)/hMECP2 has been shown to extend the lifespan of Mecp2^-/y mice, but this delivery route induces liver toxicity in wild-type (WT) mice. To reduce peripheral transgene expression, we explored the safety and efficacy of AAV9/hMECP2 injected into the cisterna magna (ICM). AAV9/hMECP2 (1 × 10¹² viral genomes [vg]; ICM) extended Mecp2^-/y survival but aggravated hindlimb clasping and abnormal gait phenotypes. In WT mice, 1 × 10¹² vg of AAV9/hMECP2 induced clasping and abnormal gait. A lower dose mitigated these adverse phenotypes but failed to extend survival of Mecp2^-/y mice. Thus, ICM delivery of this vector is impractical

SUBMITTER: Sinnett SE 

PROVIDER: S-EPMC5424572 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature