Receptor-mediated DNA delivery approaches to human gene therapy.
The current non-viral approaches to gene therapy are presented with a particular emphasis on receptor-mediated DNA delivery and the recent advances made that make this approach an attractive alternative to viral-based vector systems. The general strategy for receptor-mediated DNA delivery involves condensing DNA via electrostatic interaction with a polycation, e.g. polylysine, chemically linked to a cell binding ligand, e.g. transferrin. The potency of this delivery system has recently been improved by incorporating an endosome disrupting (endosomolytic) agent into the DNA-complex, such as adenovirus particles, which enhances release into the cytoplasm. Therefore, the approach now is to mimic viral entry mechanisms, e.g. by incorporating a synthetic peptide with endosomolytic activity, and, in effect, manufacture a synthetic virus.
Phillips
S C
SC
Central Research Division, Pfizer Limited, Sandwich, Kent, U.K.
D000818:Animals; D004247:DNA / Q000378:metabolism*; D005544:Forecasting; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism*
D011956:Receptors, Cell Surface; D004247:DNA