Evolving Phage Vectors for Cell Targeted Gene Delivery

Authors: Larocca D.; Brug M.A.; Jensen-pergakes K.; Ravey E.Prenn; Gonzalez A.Maria; Baird A.

Source: Current Pharmaceutical Biotechnology, Volume 3, Number 1, March 2002 , pp. 45-57(13)

Publisher: Bentham Science Publishers

Abstract:

We adapted filamentous phage vectors for targeted gene delivery to mammalian cells by inserting a mammalian reporter gene expression cassette (GFP) into the vector backbone and fusing the pIII coat protein to a cell targeting ligand (i.e. FGF2, EGF). Like transfection with animal viral vectors, targeted phage gene delivery is concentration, time, and ligand dependent. Importantly, targeted phage particles are specific for the appropriate target cell surface receptor. Phage have distinct advantages over existing gene therapy vectors because they are simple, economical to produce at high titer, have no intrinsic tropism for mammalian cells, and are relatively simple to genetically modify and evolve. Initially transduction by targeted phage particles was low resulting in foreign gene expression in 1-2 percent of transfected cells. We increased transduction efficiency by modifying both the transfection protocol and vector design. For example, we stabilized the display of the targeting ligand to create multivalent phagemid-based vectors with transduction efficiencies of up to 45 percent in certain cell lines when combined with genotoxic treatment. Taken together, these studies establish that the efficiency of phage-mediated gene transfer can be significantly improved through genetic modification. We are currently evolving phage vectors

Keywords: Phage Vectors; Gene Delivery; single-chain antibody; adenoassociated virus (AAV)

Language: English

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1389201023378490

Publication date: 2002-03-01

• Current Pharmaceutical Biotechnology aims to cover all the latest and outstanding developments in Pharmaceutical Biotechnology. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in both pre-clinical and clinical areas of Pharmaceutical Biotechnology. Current Pharmaceutical Biotechnology is an essential journal for academic, clinical, government and pharmaceutical scientists who wish to be kept informed and up-to-date with the latest and most important developments.

• In this: publication
• By this: publisher
• In this Subject: Nutrition & Food ,  Biotechnology ,  Pharmacology
• By this author: Larocca D. ;  Brug M.A. ;  Jensen-pergakes K. ;  Ravey E.Prenn ;  Gonzalez A.Maria ;  Baird A.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers