Impact of age and vector construct on striatal and nigral transgene expression | Zendy

Nicole K. Polinski | Zendy; Fredric P. Manfredsson | Zendy; Matthew J. Benskey | Zendy; D. Luke Fischer | Zendy; Christopher J. Kemp | Zendy; Kathy SteeceCollier | Zendy; Ivette M. Sandoval | Zendy; Katrina L. Paumier | Zendy; Caryl E. Sortwell | Zendy

AI Assistant Blog Pricing

Home ZAIA Blog

Open Access

Impact of age and vector construct on striatal and nigral transgene expression

Author(s) -

Nicole K. Polinski,

Fredric P. Manfredsson,

Matthew J. Benskey,

D. Luke Fischer,

Christopher J. Kemp,

Kathy SteeceCollier,

Ivette M. Sandoval,

Katrina L. Paumier,

Caryl E. Sortwell

Publication year - 2016

Publication title -

molecular therapy — methods and clinical development

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.285

H-Index - 32

ISSN - 2329-0501

DOI - 10.1038/mtm.2016.82

Subject(s) - transgene , green fluorescent protein , biology , genetic enhancement , substantia nigra , tropism , striatum , in situ hybridization , viral vector , microbiology and biotechnology , gene expression , recombinant dna , immunology , neuroscience , virus , gene , dopaminergic , dopamine , genetics

Therapeutic protein delivery using viral vectors has shown promise in preclinical models of Parkinson's disease (PD) but clinical trial success remains elusive. This may partially be due to a failure to include advanced age as a covariate despite aging being the primary risk factor for PD. We investigated transgene expression following intracerebral injections of recombinant adeno-associated virus pseudotypes 2/2 (rAAV2/2), 2/5 (rAAV2/5), 2/9 (rAAV2/9), and lentivirus (LV) expressing green fluorescent protein (GFP) in aged versus young adult rats. Both rAAV2/2 and rAAV2/5 yielded lower GFP expression following injection to either the aged substantia nigra or striatum. rAAV2/9-mediated GFP expression was deficient in the aged striatonigral system but displayed identical transgene expression between ages in the nigrostriatal system. Young and aged rats displayed equivalent GFP levels following LV injection to the striatonigral system but LV-delivered GFP was deficient in delivering GFP to the aged nigrostriatal system. Notably, age-related transgene expression deficiencies revealed by protein quantitation were poorly predicted by GFP-immunoreactive cell counts. Further, in situ hybridization for the viral CβA promoter revealed surprisingly limited tropism for astrocytes compared to neurons. Our results demonstrate that aging is a critical covariate to consider when designing gene therapy approaches for PD

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research