We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Assessment of the Safety and Biodistribution of a Regulated AAV2 Gene Transfer Vector after Delivery to Murine Submandibular Glands.
- Authors
Zheng, Changyu; Voutetakis, Antonis; Goldstein, Benjamin; Afione, Sandra; Rivera, Victor M.; Clackson, Tim; Wenk, Martin L.; Boyle, Molly; Nyska, Abraham; Chiorini, John A.; Vallant, Molly; Irwin, Richard D.; Baum, Bruce J.
- Abstract
Clinical gene transfer holds promise for the treatment of many inherited and acquired disorders. A key consideration for all clinical gene transfer applications is the tight control of transgene expression. We have examined the safety and biodistribution of a serotype 2, recombinant adeno-associated viral (AAV2) vector that encodes a rapamycin-responsive chimeric transcription factor, which regulates the expression of a therapeutic transgene (human erythropoietin [hEpo]). The vector, AAV2-TF2.3w-hEpo (2.5 × 107–2.5 × 1010 particles), was administered once to a single submandibular gland of male and female mice and mediated hEpo expression in vivo following a rapamycin injection but not in its absence. Control (saline treated) and vector-treated animals maintained their weight, and consumed food and water, similarly. Vector delivery led to no significant toxicological effects as judged by hematology, clinical chemistry, and gross and microscopic pathology evaluations. On day 3 after vector delivery, vector copies were not only abundant in the targeted right submandibular gland but also detected in multiple other tissues. Vector was cleared from the targeted gland much more rapidly in female mice than in male mice. Overall, our results are consistent with the notion that administration of the AAV2-TF2.3w-hEpo vector to salivary glands posed no significant risk in mice.
- Subjects
SUBMANDIBULAR gland; GENETIC transformation; GENETIC disorder treatment; TRANSGENE expression; GENETIC regulation; SALIVARY glands; RAPAMYCIN; LABORATORY mice
- Publication
Toxicological Sciences, 2011, Vol 123, Issue 1, p247
- ISSN
1096-6080
- Publication type
Article
- DOI
10.1093/toxsci/kfr144