Aug 19, 2003

Polyhistidine-PEG:DNA nanocomposites for gene delivery

Biomaterials
David PutnamRobert Langer

Abstract

Complexation of plasmid DNA with polycations is a popular method by which to transfer therapeutic nucleic acid sequences to cells. One caveat of the approach is that the positive zeta potential of the complexes facilitates interaction with blood constituents, leading to serum protein adsorption and complement activation. As a countermeasure, investigators have developed polycations combined with polyethylene glycol (PEG) to create complexes with reduced protein adsorption potential. We have designed and synthesized PEG-polyhistidine conjugates to evaluate the material class as potential gene delivery vehicles. Two conjugate architectures (comb-shaped and linear A-B block copolymers) were synthesized and formulated with plasmid DNA. The complexes were characterized with respect to DNA complexation capacity, hydrodynamic diameter, zeta potential, in vitro cytotoxicity and transfection capacity in a model cell line. PEG content of the conjugate significantly influenced the hydrodynamic diameter of the DNA:conjugate composite in aqueous solution. For comb-shaped conjugates steric hindrance attributed to PEG led to a direct relationship between the PEG content and the complex size. Both architectures could condensed plasmid DNA into...Continue Reading

Mentioned in this Paper

Deoxyribonuclease I
Transfection
Histidine
AP5Z1 gene
Complex (molecular entity)
Polyhistidine, (D)-isomer
Serum Proteins
Adsorption
Cytotoxicity
Combid

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