Premium
Charge‐resersible lipids for DNA delivery
Author(s) -
Prata Carla A Hernandez,
Barthelemy Philippe,
Li Yougen,
Luo Dan,
McIntosh Thomas J,
Lee Stephen J,
Grinstaff Mark W
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a73-b
Subject(s) - transfection , dna , ethidium bromide , gene delivery , chemistry , biochemistry , endosome , biophysics , intracellular , biology , gene
One of the critical steps limiting the efficiency of non‐viral gene delivery is the intracellular release of DNA from the vector complex. The complex should be stable enough to prevent DNA degradation but also dissociate from the DNA once inside the endosome for subsequent transcription. Degradation of the synthetic vector is also required to reduce cytotoxicity and increase the life‐time of transfected cells. To facilitate the escape of DNA from the DNA‐lipid complex in the cell, and thus improve transfection efficiency, we have developed esterase sensitive cationic lipids. These lipids form a strong complex with DNA. Once in the endosome, esterases hydrolyze the terminal ester linkage of the lipid affecting a change in overall lipid charge from cationic to anionic. This charge reversal transition releases the DNA from the lipids. These charge‐reversal lipids were synthesized and characterized. The complexation and dissociation of the lipid to the DNA was monitorated using an ethidium bromide displacement assay. The supramolecular lipid/DNA complexes were also characterized by TEM and X‐ray scattering. Successful gene transfection was observed with this new class of lipids.