Efficient in vitro gene delivery by hybrid biopolymer/virus nanobiovectors

Rahul Keswani; Kai Su; Daniel W. Pack

doi:10.1016/j.jconrel.2014.06.060

Efficient in vitro gene delivery by hybrid biopolymer/virus nanobiovectors

Rahul Keswani
, Kai Su
, Daniel W. Pack

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

Recombinant retroviruses provide highly efficient gene delivery and the potential for sustained gene expression, but suffer from significant disadvantages including low titer, expensive production, poor stability and limited flexibility for modification of tropism. In contrast, polymer-based vectors are more robust and allow cell- and tissue-specific deliveries via conjugation of ligands, but are comparatively inefficient. The design of hybrid gene delivery agents comprising both virally derived and synthetic materials (nanobiovectors) represents a promising approach to development of safe and efficient gene therapy vectors. Non-infectious murine leukemia virus-like particles (M-VLPs) were electrostatically complexed with chitosan (χ) to replace the function of the viral envelope protein. At optimal fabrication conditions and compositions, ranging from 6 to 9 μg chitosan/10⁹ M-VLPs at 10 × 10⁹ M-VLPs/ml to 40 μg chitosan/10 ⁹ M-VLPs at 2.5 × 10⁹ M-VLPs/ml, χ/M-VLPs were ∼ 300-350 nm in diameter and exhibited efficient transfection similar to amphotropic MLV vectors. In addition, these nanobiovectors were non-cytotoxic and provided sustained transgene expression for at least three weeks in vitro. This combination of biocompatible synthetic agents with inactive viral particles to form a highly efficient hybrid vector is a significant extension in the development of novel gene delivery platforms.

Original language	English
Pages (from-to)	40-46
Number of pages	7
Journal	Journal of Controlled Release
Volume	192
DOIs	https://doi.org/10.1016/j.jconrel.2014.06.060
State	Published - Oct 28 2014

Bibliographical note

Funding Information:
This work was partially supported by the National Science Foundation ( BES 06-02636 ) and National Institutes of Health ( GM085222 ). In addition, we thank S. Mattick at the Cell Culture Media Facility at the University of Illinois for helping with preparation of cell media. Flow cytometry was performed at the Roy J. Carver Biotechnology Center Flow Cytometry Facility, University of Illinois. TEM was performed with the assistance of L. Miller at the Frederick Seitz Materials Research Laboratory, University of Illinois. q-PCR was performed at the Institute of Genomic Biology Core Facilities, University of Illinois.

Funding

This work was partially supported by the National Science Foundation ( BES 06-02636 ) and National Institutes of Health ( GM085222 ). In addition, we thank S. Mattick at the Cell Culture Media Facility at the University of Illinois for helping with preparation of cell media. Flow cytometry was performed at the Roy J. Carver Biotechnology Center Flow Cytometry Facility, University of Illinois. TEM was performed with the assistance of L. Miller at the Frederick Seitz Materials Research Laboratory, University of Illinois. q-PCR was performed at the Institute of Genomic Biology Core Facilities, University of Illinois.

Funders	Funder number
U.S. Department of Energy Chinese Academy of Sciences Guangzhou Municipal Science and Technology Project Oak Ridge National Laboratory Extreme Science and Engineering Discovery Environment National Science Foundation National Energy Research Scientific Computing Center National Natural Science Foundation of China	BES 06-02636
U.S. Department of Energy Chinese Academy of Sciences Guangzhou Municipal Science and Technology Project Oak Ridge National Laboratory Extreme Science and Engineering Discovery Environment National Science Foundation National Energy Research Scientific Computing Center National Natural Science Foundation of China
National Institutes of Health (NIH)
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences	R01GM085222
National Institute of General Medical Sciences DP2GM119177 Sophie Dumont National Institute of General Medical Sciences

Keywords

Chitosan
Gene delivery
Gene therapy
Hybrid vectors
Retrovirus

ASJC Scopus subject areas

Pharmaceutical Science

Access to Document

10.1016/j.jconrel.2014.06.060

Cite this

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title = "Efficient in vitro gene delivery by hybrid biopolymer/virus nanobiovectors",

abstract = "Recombinant retroviruses provide highly efficient gene delivery and the potential for sustained gene expression, but suffer from significant disadvantages including low titer, expensive production, poor stability and limited flexibility for modification of tropism. In contrast, polymer-based vectors are more robust and allow cell- and tissue-specific deliveries via conjugation of ligands, but are comparatively inefficient. The design of hybrid gene delivery agents comprising both virally derived and synthetic materials (nanobiovectors) represents a promising approach to development of safe and efficient gene therapy vectors. Non-infectious murine leukemia virus-like particles (M-VLPs) were electrostatically complexed with chitosan (χ) to replace the function of the viral envelope protein. At optimal fabrication conditions and compositions, ranging from 6 to 9 μg chitosan/109 M-VLPs at 10 × 109 M-VLPs/ml to 40 μg chitosan/10 9 M-VLPs at 2.5 × 109 M-VLPs/ml, χ/M-VLPs were ∼ 300-350 nm in diameter and exhibited efficient transfection similar to amphotropic MLV vectors. In addition, these nanobiovectors were non-cytotoxic and provided sustained transgene expression for at least three weeks in vitro. This combination of biocompatible synthetic agents with inactive viral particles to form a highly efficient hybrid vector is a significant extension in the development of novel gene delivery platforms.",

keywords = "Chitosan, Gene delivery, Gene therapy, Hybrid vectors, Retrovirus",

author = "Rahul Keswani and Kai Su and Pack, \{Daniel W.\}",

note = "Funding Information: This work was partially supported by the National Science Foundation ( BES 06-02636 ) and National Institutes of Health ( GM085222 ). In addition, we thank S. Mattick at the Cell Culture Media Facility at the University of Illinois for helping with preparation of cell media. Flow cytometry was performed at the Roy J. Carver Biotechnology Center Flow Cytometry Facility, University of Illinois. TEM was performed with the assistance of L. Miller at the Frederick Seitz Materials Research Laboratory, University of Illinois. q-PCR was performed at the Institute of Genomic Biology Core Facilities, University of Illinois. ",

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AB - Recombinant retroviruses provide highly efficient gene delivery and the potential for sustained gene expression, but suffer from significant disadvantages including low titer, expensive production, poor stability and limited flexibility for modification of tropism. In contrast, polymer-based vectors are more robust and allow cell- and tissue-specific deliveries via conjugation of ligands, but are comparatively inefficient. The design of hybrid gene delivery agents comprising both virally derived and synthetic materials (nanobiovectors) represents a promising approach to development of safe and efficient gene therapy vectors. Non-infectious murine leukemia virus-like particles (M-VLPs) were electrostatically complexed with chitosan (χ) to replace the function of the viral envelope protein. At optimal fabrication conditions and compositions, ranging from 6 to 9 μg chitosan/109 M-VLPs at 10 × 109 M-VLPs/ml to 40 μg chitosan/10 9 M-VLPs at 2.5 × 109 M-VLPs/ml, χ/M-VLPs were ∼ 300-350 nm in diameter and exhibited efficient transfection similar to amphotropic MLV vectors. In addition, these nanobiovectors were non-cytotoxic and provided sustained transgene expression for at least three weeks in vitro. This combination of biocompatible synthetic agents with inactive viral particles to form a highly efficient hybrid vector is a significant extension in the development of novel gene delivery platforms.

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Efficient in vitro gene delivery by hybrid biopolymer/virus nanobiovectors

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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