| Literature DB >> 30864850 |
Peters Tobias1,2, Seitz Immanuel Philipp1, Michalakis Stylianos3, Biel Martin3, Wilhelm Barbara2, Reichel Felix1, Ochakovski Guy Alexander1, Zrenner Eberhart4,5, Ueffing Marius5, Korbmacher Birgit6, Korte Sven6, Bartz-Schmidt Karl Ulrich1, Fischer Manuel Dominik1.
Abstract
The purpose of this study was to examine the toxicity and side effects of a recombinant adeno-associated virus 8 (AAV8) vector, aimed to treat cyclic nucleotide gated channel alpha 3 (CNGA3)-linked achromatopsia, after a single subretinal administration in cynomolgus macaques. Animals were followed in two studies: a 13-week study with 22 animals and a 28-day study with 12 animals. Both groups were divided into subgroups receiving either vehicle only, a low (1 × 1011 vector genomes (vg)), or a high dose (1 × 1012 vg) of rAAV.hCNGA3. In the 13-week study, an extra group received single high-dose intravitreal injections. Here we present the group results of the histological examinations carried out after necropsy from the 28-day study, the retinal functional (electroretinography) in the 13-week study, and clinical observations from both studies. Treatment-related adverse effects were not found, and parameter changes were mostly related to the surgical procedure. The treatment of achromatopsia with rAAV.hCNGA3 is therefore deemed safe to apply to humans.Entities:
Keywords: AAV8; achromatopsia; inlife assessment; macaques; toxicity
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Year: 2019 PMID： 30864850 DOI： 10.1089/humc.2018.188
Source DB: PubMed Journal: Hum Gene Ther Clin Dev ISSN： 2324-8637 Impact factor: 5.032