Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses.

MARAL YOLAMANOVA; CHRISTOPH MEIER; ALEXEY K. SHAYTAN; VIRAG VAS; CARLOS W. BERTONCINI; FRANZISKA ARNOLD; ONOFRIO ZIRAFI; SHARIQ M. USMANI; JANIS A. MÜLLER; DANIEL SAUTER; CHRISTINE GOFFINET; DAVID PALESCH; PAUL WALTHER; NADIA R. ROAN; HARTMUT GEIGER; OLEG LUNOV; THOMAS SIMMET; JENS BOHNE; HUBERT SCHREZENMEIER; KLAUS SCHWARZ; LUDGER STÄNDKER; WOLF-GEORG FORSSMANN; XAVIER SALVATELLA; PAVEL G. KHALATUR; ALEXEI R. KHOKHLOV; TUOMAS P. J. KNOWLES; TANJA WEIL; FRANK KIRCHHOFF ; JAN MÜNCH

NATURE NANOTECHNOLOGY

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2013 vol. 8 p. 130 - 136

1748-3387

Inefficient gene transfer and low virion concentrations are common limitations of retroviral transduction1. 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 cells2, 3, 4, 5, 6, 7, 8. 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.