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Evaluation of cell-penetrating peptide/adenovirus particles for transduction of CAR-negative cells.

Authors :
Nigatu AS
Vupputuri S
Flynn N
Neely BJ
Ramsey JD
Source :
Journal of pharmaceutical sciences [J Pharm Sci] 2013 Jun; Vol. 102 (6), pp. 1981-1993. Date of Electronic Publication: 2013 Apr 16.
Publication Year :
2013

Abstract

Adenovirus (Ad) is a promising gene therapy vector, and is used currently in more than 23% of clinical gene therapy trials. The viral vector, however, has drawbacks such as immunogenicity, promiscuous tropism, and the inability to infect certain types of cells. The focus of this work was to develop an improved vector through electrostatic formation of a complex between negatively charged Ad and positively charged cell-penetrating peptides (CPPs), including Tat, Penetratin, polyarginine, and Pep1. The resulting complexes were demonstrated to be capable of transducing cells that lack the coxsackie-adenovirus receptor (CAR), and are otherwise difficult to infect with native Ad. The transduction efficiency of the complexes was optimized by varying the multiplicity of infection, complex formation time, and ratio of CPPs to Ad, which improved the transduction efficiency of CPP/Ad on CAR-negative cells more than 100-fold compared with unmodified Ad. The size of the CPP/Ad complex was initially less than 300 nm, but stability studies performed in the presence of serum indicate that the complex aggregates with serum after an extended period of time. The results of the current study indicate that electrostatic modification of Ad with CPPs provides a relevant platform for developing effective Ad-based gene therapy vectors.<br /> (Copyright © 2013 Wiley Periodicals, Inc.)

Details

Language :
English
ISSN :
1520-6017
Volume :
102
Issue :
6
Database :
MEDLINE
Journal :
Journal of pharmaceutical sciences
Publication Type :
Academic Journal
Accession number :
23592439
Full Text :
https://doi.org/10.1002/jps.23556