AAV2-L1
Information
Call for collaboration proposals
We share a lung-specific, AAV-based gene therapy vector for collaborative research towards pulmonary indications. After intravenous administration, the AAV2-L1 capsid variant shows a highly specific tropism for the mouse lung, where it efficiently and preferentially transduces the pulmonary vascular endothelial cells. This vector is suited to testing new therapeutic concepts for the lung. We invite scientists to submit proposals containing a testable hypothesis using gene constructs that could be packaged in the AAV2-L1 vector.
Partners would gain privileged access to our unique lung-specific gene therapy vector and collaborate with Boehringer Ingelheim scientists who have cutting-edge gene therapy and drug discovery expertise. Funding requests up to €200.000 can be submitted as part of the proposal and will be considered for selected projects. Moreover, your gene construct will be packaged in the AAV2-L1 vector and provided free of charge in the amount required for the experiments in rodents.
Submissions for collaborations can only be considered if they arrive no later than April 12, 2019 23.59 pm PST.
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Target information
AAV2-L1 was identified by a NGS-guided in vivo selection of AAV2-dervied capsid variants with a lung tropism and high transduction efficiency (see Körbelin J et al, Mol Ther. 2016 Jun;24(6):1050-1061). This tropism is conferred by displaying a hepta-peptide (ESGHGYF) on the AAV2 capsid surface. Specifically, AAV2-ESGHGYF is selectively recognized and taken-up by the pulmonary vascular endothelium by a currently undefined receptor. This vector is suited to the in vivo delivery of a gene construct to the lungs of mice.
Gene construct
Gene constucts up to the 4.7 kb packaging limit (incl. promoter and regulatory elements) can be inserted into the AAV2-L1 capsid. It is suitable for gene replacement, miRNA/RNAi expression and CRISPR/Cas cargos.
In vitro transduction of cells
AAV2-L1 displays very inefficient transduction of commonly used cell lines in vitro.
In vivo tissue transduction and expression timeframe
AAV2-L1 shows a selective transduction of pulmonary vascular endothelial cells after intravenous or intraperitoneal administration. Maximal lung transduction was achieved by 14 days and was maintained for at least 244 days post-dosing.
Lung-selectivity
AAV2-L1 demonstrated a »100-fold tropism for lung when compared to the wild-type AAV2 14 days after intravenous administration to mice.
Summary
We share a unique lung-specific AAV vector for collaborative research on novel gene therapy concepts for pulmonary disease. Partners would gain privileged access to our gene therapy vector and collaborate with Boehringer Ingelheim scientists. Funding of up to €200.000 is available for each selected proposal. We invite scientists to submit proposals containing a testable hypothesis using our lung-specific AAV vector (AAV2-L1).
References
Pulmonary Targeting of Adeno-associated Viral Vectors by Next-generation Sequencing-guided Screening of Random Capsid Displayed Peptide Libraries
Körbelin J, Sieber T, Michelfelder S, Lunding L, Spies E, Hunger A, Alawi M, Rapti K, Indenbirken D, Müller OJ, Pasqualini R, Arap W, Kleinschmidt JA, Trepel M.
Mol Ther., 2016, Jun;24(6):1050-1061.