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Retina transduction by rAAV2 after intravitreal injection: comparison between mouse and rat.

Gene therapy (2019-09-29)
Mariana S Dias, Victor G Araujo, Taliane Vasconcelos, Qiuhong Li, William W Hauswirth, Rafael Linden, Hilda Petrs-Silva

Adeno-associated virus vectors (rAAV) are currently the most common vehicle used in clinical trials of retinal gene therapy, usually delivered through subretinal injections to target cells of the outer retina. However, targeting the inner retina requires intravitreal injections, a simple and safe procedure, which is effective for transducing the rodent retina, but still of low efficiency in the eyes of primates. We investigated whether adjuvant pharmacological agents may enhance rAAV transduction of the retinas of mouse and rat after intravitreal delivery. Tyrosine kinase inhibitors were highly efficient in mice, especially imatinib and genistein, and promoted transduction even of the outer retina. In rats, however, we report that they were not effective. Even with direct proteasomal inhibition in rats, the effects upon transduction were only minimal and restricted to the inner retina. Even tyrosine capsid mutant rAAVs in rats had a transduction profile similar to wtAAV. Thus, the differences between mouse and rat, in both eye size and the inner limiting membrane, compromise the efficiency of AAV vectors penetration from the vitreous into the retina, and impact the efficacy of strategies developed to enhance intravitreal retinal rAAV transduction. Further improvement of strategies, then are required.

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Product Description

PP2 - CAS 172889-27-9 - Calbiochem, PP2, CAS 172889-27-9, is a potent, reversible, ATP-competitive, inhibitor of the Src family of protein tyrosine kinases (IC₅₀ = 4, 5, 5, &100 nM for p56lck, p59fynT, Hck, & Src, respectively).
AG 1478 - CAS 175178-82-2 - Calbiochem, A cell-permeable, reversible, ATP-competitive, highly potent and selective inhibitor of epidermal growth factor receptor kinase versus HER2-neu and platelet-derived growth factor receptor kinase.
AG 1296 - CAS 146535-11-7 - Calbiochem, A cell-permeable, reversible, and ATP-competitive, inhibitor of PDGF receptor kinase and blocks signaling of human PDGF α-receptors and β-receptors.
Human VEGFR1 ELISA Kit, for cell culture supernatants, plasma, and serum samples