title: PEGylated Cationic Serum Albumin for Boosting Retroviral Gene Transfer.
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.
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Palesch
authors.affiliation: Institute of Organic Chemistry III/Macromolecular Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Boldt
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
authors.forename: Janis A
authors.initials: JA
authors.lastname: Müller
authors.affiliation: Institute of Organic Chemistry III/Macromolecular Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Eisele
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Stürzel
authors.affiliation: Institute of Organic Chemistry III/Macromolecular Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany.
authors.forename: Yuzhou
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081, Ulm, Germany. jan.muench@uni-ulm.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Münch
authors.affiliation: Institute of Organic Chemistry III/Macromolecular Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081, Ulm, Germany. tanja.weil@uni-ulm.de.
authors.forename: Tanja
authors.initials: T
authors.lastname: Weil
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011092:Polyethylene Glycols / Q000737:chemistry*; D012190:Retroviridae / Q000235:genetics*; D012709:Serum Albumin / Q000737:chemistry*
chemical_list: D002412:Cations; D012709:Serum Albumin; D011092:Polyethylene Glycols
keywords: PEGylation; human serum albumin; protein modifications; retroviral gene therapy; retroviral gene transduction enhancement; viruses