title: Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses.
abstract: Inefficient gene transfer and low virion concentrations are common limitations of retroviral transduction. We and others have previously shown that peptides derived from human semen form amyloid fibrils that boost retroviral gene delivery by promoting virion attachment to the target cells. However, application of these natural fibril-forming peptides is limited by moderate efficiencies, the high costs of peptide synthesis, and variability in fibril size and formation kinetics. Here, we report the development of nanofibrils that self-assemble in aqueous solution from a 12-residue peptide, termed enhancing factor C (EF-C). These artificial nanofibrils enhance retroviral gene transfer substantially more efficiently than semen-derived fibrils or other transduction enhancers. Moreover, EF-C nanofibrils allow the concentration of retroviral vectors by conventional low-speed centrifugation, and are safe and effective, as assessed in an ex vivo gene transfer study. Our results show that EF-C fibrils comprise a highly versatile, convenient and broadly applicable nanomaterial that holds the potential to significantly facilitate retroviral gene transfer in basic research and clinical applications.
authors: Institute of Molecular Virology, Ulm University Medical Center, Meyerhofstrasse 1, 89081 Ulm, Germany.
authors: Maral
authors: M
authors: Yolamanova
authors: Christoph
authors: C
authors: Meier
authors: Alexey K
authors: AK
authors: Shaytan
authors: Virag
authors: V
authors: Vas
authors: Carlos W
authors: CW
authors: Bertoncini
authors: Franziska
authors: F
authors: Arnold
authors: Onofrio
authors: O
authors: Zirafi
authors: Shariq M
authors: SM
authors: Usmani
authors: Janis A
authors: JA
authors: Müller
authors: Daniel
authors: D
authors: Sauter
authors: Christine
authors: C
authors: Goffinet
authors: David
authors: D
authors: Palesch
authors: Paul
authors: P
authors: Walther
authors: Nadia R
authors: NR
authors: Roan
authors: Hartmut
authors: H
authors: Geiger
authors: Oleg
authors: O
authors: Lunov
authors: Thomas
authors: T
authors: Simmet
authors: Jens
authors: J
authors: Bohne
authors: Hubert
authors: H
authors: Schrezenmeier
authors: Klaus
authors: K
authors: Schwarz
authors: Ludger
authors: L
authors: Ständker
authors: Wolf-Georg
authors: WG
authors: Forssmann
authors: Xavier
authors: X
authors: Salvatella
authors: Pavel G
authors: PG
authors: Khalatur
authors: Alexei R
authors: AR
authors: Khokhlov
authors: Tuomas P J
authors: TP
authors: Knowles
authors: Tanja
authors: T
authors: Weil
authors: Frank
authors: F
authors: Kirchhoff
authors: Jan
authors: J
authors: Münch
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000235:genetics; D000818:Animals; D002498:Centrifugation; D015316:Genetic Therapy; D005822:Genetic Vectors; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D006801:Humans; D051379:Mice; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D012190:Retroviridae / Q000235:genetics*; D017550:Spectroscopy, Fourier Transform Infrared; D014161:Transduction, Genetic; D014771:Virion / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D014961:X-Ray Diffraction
chemical_list: D000682:Amyloid; D015699:HIV Envelope Protein gp120; D010455:Peptides; C514793:gp120 protein, Human immunodeficiency virus 1