ArticleMolecular therapy. Methods & clinical development2019
Site-Specific Glycation and Chemo-enzymatic Antibody Sortagging for the Retargeting of rAAV6 to Inflamed Endothelium.
Article in Molecular therapy. Methods & clinical development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Advances in endothelial cell targeting by AAV vectors.Acta biochimica Polonica · 2026Review
- Emerging trends in virus and virus-like particle gene therapy delivery to the brain.Molecular therapy. Nucleic acids · 2024Review
- Chemical approaches to probe and engineer AAV vectors.Nanoscale · 2024Review
- Delivering CRISPR to the HIV-1 reservoirs.Frontiers in microbiology · 2024Review
- Technological advances in the use of viral and non-viral vectors for delivering genetic and non-genetic cargos for cancer therapy.Drug delivery and translational research · 2023Review
- Chemical modification of AAV9 capsid with N-ethyl maleimide alters vector tissue tropism.Scientific reports · 2023Article
- Review
- Fast and high-throughput LC-MS characterization, and peptide mapping of engineered AAV capsids using LC-MS/MS.Molecular therapy. Methods & clinical development · 2022Article
- Fantastic AAV Gene Therapy Vectors and How to Find Them-Random Diversification, Rational Design and Machine Learning.Pathogens (Basel, Switzerland) · 2022Review
- Endothelial Retargeting of AAV9 In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Chemical Modifications of the Capsid for Redirecting and Improving the Efficacy of Adeno-Associated Virus Vectors.Human gene therapy · 2021Article
- Alginate hydrogel polymers enable efficient delivery of a vascular-targeted AAV vector into aortic tissue.Molecular therapy. Methods & clinical development · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene therapy holds great potential for conditions such as cardiovascular disease, including atherosclerosis and also vascular cancers, yet available vectors such as the adeno-associated virus (rAAV) transduce the vasculature poorly. To enable retargeting, a single-chain antibody (scFv) that binds to the vascular cell-adhesion molecule (VCAM-1) overexpressed at areas of endothelial inflammation was site specifically and covalently conjugated to the exterior of rAAV6. To achieve conjugation, the scFv was functionalized with an orthogonal click chemistry group. This conjugation utilized site-specific sortase A methodology, thus preserving scFv binding capacity to VCAM-1. The AAV6 was separately functionalized with 4-azidophenyl glyoxal (APGO) via covalent adducts to arginine residues in the capsid's heparin co-receptor binding region. APGO functionalization removed native tropism, greatly reducing rAAV6-GFP transduction into all cells tested, and the effect was similar to the inhibition seen in the presence of heparin. Utilizing the incorporated functionalizations, the scFv was then covalently conjugated to the exterior of rAAV6 via strain-promoted azide-alkyne cycloaddition (SPAAC). With both the removal of native heparin tropism and the addition of VCAM-1 targeting, rAAV6 transduction of endothelial cells was greatly enhanced compared to control cells. Thus, this novel and modular targeting system could have further application in re-directing AAV6 toward inflamed endothelium for therapeutic use.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.