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.

Cryo-EM reveals the steric zipper structure of a light chain-derived amyloid fibril

“…Peptide fibrils with amyloid properties may also have functional properties in vivo (1) or be relevant for a broad range of possible biotechnological applications, such as viral transfection enhancers, templated metal wires, and peptide scaffolds for cell growth (32)(33)(34)(35). In our present analysis of the AL1 peptide fibrils, we are able to rationalize the observed structure in terms of a few basic chemical interactions that may permit the assembly of other fibril structures from designed peptides.…”

Designed amyloid fibers as materials for selective carbon dioxide capture

“…Applications of amyloid fibers have been explored in the fields including conductive nanowires (34), nanostructured protein films (35), light-harvesting nano-device (36,37), and retroviral gene transfer boosting (38). The properties demonstrated here of amyloid fibers for carbon dioxide capture fall short of those needed in a practical material operating in the demanding conditions of water, acid, and temperature of flue gas.…”

Molecular Determinants of Vectofusin-1 and Its Derivatives for the Enhancement of Lentivirally Mediated Gene Transfer into Hematopoietic Stem/Progenitor Cells

“…Lipofectin or Lipofectamine (17,18)), or cationic peptides/proteins (e.g. fibronectin fragments (19 -21), protamine sulfate (22), prostatic acid phosphatase fragments (23), or HIV-1 gp41-and gp120-derived peptides (24,25)). These mostly cationic additives have the capacity to neutralize membrane charges and promote viral adhesion, viral fusion (2), virus aggregation (26), and/or virus pulldown through the formation of nanofibrillar structures (27).…”