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Peptide nanofibrils as enhancers of retroviral gene transfer



Amyloid fibrils are polypeptide-based polymers that are typically associated with neurodegenerative disorders such as Alzheimer's disease. More recently, it has become clear that amyloid fibrils also fulfill functional roles in hormone storage and biosynthesis. Furthermore, it has been demonstrated that semen contains abundant levels of polycationic amyloid fibrils. The natural role of these seminal amyloids remains elusive. Strikingly, however, they drastically enhance HIV-1 infection and may be exploited by the virus to increase its sexual transmission rate. Their strong activity in enhancing HIV-1 infection suggests that seminal amyloid might also promote transduction by retroviral vectors. Indeed, SEVI (semen-derived enhancer of virus infection), the best characterized seminal amyloid, boosts retroviral gene transfer more efficiently than conventional additives. However, the use of SEVI as laboratory tool for efficient retroviral gene transfer is limited because the polypeptide monomers are relatively expensive to produce. Furthermore, standardized production of SEVI fibrils with similar high activities is difficult to achieve because of the stochastic nature of the amyloid assembly process. These obstacles can be overcome by recently identified smaller peptides that spontaneously self-assemble into nanofibrils. These nanofibrils increase retroviral gene transfer even more efficiently than SEVI, are easy to produce and to handle, and seem to be safe as assessed in an ex vivo gene transfer study. Furthermore, peptide-based nanofibrils allow to concentrate viral particles by low-speed centrifugation. Specific adaption and customization of self-assembling peptides might lead to novel nanofibrils with versatile biological functions, e.g., targeted retroviral gene transfer or drug delivery.

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Conflict of interest: F. K. and J. M. hold a patent to use peptide nanofibrils to facilitate retroviral gene transfer.