PEGylated Cationic Serum Albumin for Boosting Retroviral Gene Transfer |
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Authors: | Dr. David Palesch Felix Boldt Janis A. Müller Dr. Klaus Eisele Dr. Christina M. Stürzel Dr. Yuzhou Wu Prof. Dr. Jan Münch Prof. Dr. Tanja Weil |
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Affiliation: | 1. Institute of Molecular Virology, Ulm University Medical Center, Ulm, Germany;2. Institute of Organic Chemistry III/Macromolecular Chemistry, Ulm University, Ulm, Germany |
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Abstract: | Retroviral vectors are common tools for introducing genes into the genome of a cell. However, low transduction rates are a major limitation in retroviral gene transfer, especially in clinical applications. We generated cationic human serum albumin (cHSA) protected by a shell of poly(ethylene glycol) (PEG); this significantly enhanced retroviral gene transduction with potentially attractive pharmacokinetics and low immunogenicity. By screening a panel of chemically optimized HSA compounds, we identified a very potent enhancer that boosted the transduction rates of viral vectors. Confocal microscopy revealed a drastically increased number of viral particles attached to the surfaces of target cells. In accordance with the positive net charge of cationic and PEGylated HSA, this suggests a mechanism of action in which the repulsion of the negatively charged cellular and viral vector membranes is neutralized, thereby promoting attachment and ultimately transduction. Importantly, the transduction‐enhancing PEGylated HSA derivative evaded recognition by HSA‐specific antibodies and macrophage activation. Our findings hold great promise for facilitating improved retroviral gene transfer. |
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Keywords: | human serum albumin PEGylation protein modifications retroviral gene therapy retroviral gene transduction enhancement viruses |
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