Fred Cohen
Chiron Corporation
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Chemistry & Biology | 1998
Chin-Yi Huang; Tetsuo Uno; John E. Murphy; Sandra Lee; Janice D. Hamer; Jaime Escobedo; Fred Cohen; Varavani Dwarki; Ronald N. Zuckermann
BACKGROUND Although synthetic nonviral vectors hold promise for the delivery of plasmid DNA, their gene-transfer efficiencies are far from matching those of viruses. To systematically investigate the structure-activity relationship of cationic lipids, a small library of cationic lipid-peptoid conjugates (lipitoids) was synthesized. The compounds were evaluated for their ability to form complexes with plasmid DNA and to mediate DNA transfer in vitro. RESULTS Lipid-peptoid conjugates were conveniently prepared in high yield using solid-phase synthesis. Several lipitoids condensed plasmid DNA into 100 nm spherical particles and protected the DNA and DNase digestion. A subset of lipitoids with a repeated (aminoethyl, neutral, neutral) sidechain trimer motif conjugated with dimyristoyl phosphatidyl-ethanolamine (DMPE) mediated DNA transfer with high efficiency. CONCLUSIONS Automated solid-phase synthesis of cationic lipids allowed the rapid synthesis of a diverse set of transfection reagents. The most active compound DMPE-(Nae-Nmpe-Nmpe)3 (Nae, N-aminoethyl glycine; Nmpe, N-p-methoxyphenethyl-glycine) is more efficient than lipofectin or DMRIE-C (two commercial cationic lipid transfection reagents) and is active in the presence and absence of serum. The activity in the presence of serum suggests potential for applications in vivo.
Archive | 1996
Jeffrey M. Blaney; Fred Cohen
Archive | 1996
David T. Hung; Fred Cohen; Michael A. Innis
Archive | 1996
David T. Hung; Fred Cohen
Archive | 1995
Jeffrey M. Blaney; Fred Cohen
Archive | 1997
Fred Cohen; Nathalie Dubois-Stringfellow; Varavani Dwarki; A. Michael Innis; E. John Murphy; Tetsuo Uno; Ronald Zukermann
Archive | 1997
Fred Cohen; Nathalie Dubois-Stringfellow; Varavani Dwarki; Michael A. Innis; John E. Murphy; Tetsuo Uno; Ronald Zukermann
Archive | 1997
Fred Cohen; Nathalie Dubois-Stringfellow; Varavani Dwarki; Michael A. Innis; John E. Murphy; Uno Tetsuo; Ronald Zukermann
Archive | 1997
Ronald Zukermann; Nathalie Dubois-Stringfellow; Varavani Dwarki; A Innis; E Murphy; Fred Cohen; Tetsuo Uno
Archive | 1997
Fred Cohen; Nathalie Dubois-Stringfellow; Varavani Dwarki; Michael A. Innis; John E. Murphy; Uno Tetsuo; Ronald Zukermann