TY - JOUR
T1 - Paramyxovirus-like particles as protein delivery vehicles
AU - Panthi, Santosh
AU - Schmitt, Phuong Tieu
AU - Lorenz, F. Jeffrey
AU - Stanfield, Brent A.
AU - Schmitt, Anthony P.
N1 - Funding Information:
This work was supported in part by research grant AI121880 from the National Institute of Allergy and Infectious Diseases to A.P.S., USDA award PEN04605 to A.P.S., Ximus Biosciences research grant 229004 to A.P.S., and an award from the BioStrategy Partners Germinator program to A.P.S. Additional funding was provided by PSU College of Ag. Sciences RAIN award 0400431 to A.P.S. and a PSU College of Ag. Sciences Entrepreneurship and Innovation Fellowship award to S.P.
Publisher Copyright:
© 2021 American Society for Microbiology. All Rights Reserved.
PY - 2021/10
Y1 - 2021/10
N2 - We have developed a flexible platform for delivery of proteins to target cell interiors using paramyxovirus-like particles. The key enabling feature is an appendage, 15 to 30 amino acid residues in length, that is added to cargo proteins and that induces them to bind to the viral matrix (M) protein during virus-like particle (VLP) assembly. The cargo is then incorporated within the VLPs as they bud, using the same interactions that normally direct viral genome packaging. The appendage can also serve as an epitope tag for cargo detection using a nucleocapsid (NP) protein-specific monoclonal antibody. Using this approach, we generated Renilla luciferase-loaded VLPs, green fluorescent protein-loaded VLPs, superoxide dismutase-loaded VLPs, and Cre recombinase-loaded VLPs. In each case, the VLPs could efficiently deliver their functional cargos to target cells and, in the case of Cre recombinase, to target cell nuclei. The strategy was employed using two different VLP production platforms, one based on parainfluenza virus 5 (PIV5) and the other based on Nipah virus, and in both cases efficient cargo packaging and delivery could be achieved. These findings provide a foundation for development of paramyxovirus-like particles as tools for safe and efficient delivery of therapeutic proteins to cells and tissues. IMPORTANCE Therapeutic proteins including transcription factors and genome editors have enormous clinical potential but are currently limited in part due to the challenges of safely and efficiently delivering these proteins to the interiors of target cells. Here, we have developed a new strategy for protein delivery based on manipulation of paramyxovirus genome packaging interactions.
AB - We have developed a flexible platform for delivery of proteins to target cell interiors using paramyxovirus-like particles. The key enabling feature is an appendage, 15 to 30 amino acid residues in length, that is added to cargo proteins and that induces them to bind to the viral matrix (M) protein during virus-like particle (VLP) assembly. The cargo is then incorporated within the VLPs as they bud, using the same interactions that normally direct viral genome packaging. The appendage can also serve as an epitope tag for cargo detection using a nucleocapsid (NP) protein-specific monoclonal antibody. Using this approach, we generated Renilla luciferase-loaded VLPs, green fluorescent protein-loaded VLPs, superoxide dismutase-loaded VLPs, and Cre recombinase-loaded VLPs. In each case, the VLPs could efficiently deliver their functional cargos to target cells and, in the case of Cre recombinase, to target cell nuclei. The strategy was employed using two different VLP production platforms, one based on parainfluenza virus 5 (PIV5) and the other based on Nipah virus, and in both cases efficient cargo packaging and delivery could be achieved. These findings provide a foundation for development of paramyxovirus-like particles as tools for safe and efficient delivery of therapeutic proteins to cells and tissues. IMPORTANCE Therapeutic proteins including transcription factors and genome editors have enormous clinical potential but are currently limited in part due to the challenges of safely and efficiently delivering these proteins to the interiors of target cells. Here, we have developed a new strategy for protein delivery based on manipulation of paramyxovirus genome packaging interactions.
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U2 - 10.1128/JVI.01030-21
DO - 10.1128/JVI.01030-21
M3 - Article
C2 - 34379508
AN - SCOPUS:85116344712
SN - 0022-538X
VL - 95
JO - Journal of virology
JF - Journal of virology
IS - 20
M1 - e01030-21
ER -