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.
|Number of pages||7|
|Journal||Journal of Controlled Release|
|State||Published - Oct 28 2014|
Bibliographical noteFunding 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.
- Gene delivery
- Gene therapy
- Hybrid vectors
ASJC Scopus subject areas
- Pharmaceutical Science