Gemini surfactants: new synthetic vectors for gene transfection.
The superior surfactant properties of cationic gemini surfactants are applied to the complex problem of introducing genes into cells. Of almost 250 new compounds tested, of some 20 different structural types, a majority showed very good transfection activity in vitro. The surfactant is shown to bind and compact DNA efficiently, and structural studies and calculations provide a working picture of the "lipoplex" formed. The lipoplex can penetrate the outer membranes of many cell types, to appear in the cytoplasm encapsulated within endosomes. Escape from the endosome--a key step for transfection--may be controlled by changes in the aggregation behavior of the lipoplex as the pH falls. The evidence suggests that DNA may be released from the lipoplex before entry into the nucleus, where the new gene can be expressed with high efficiency.
Kirby
Anthony J
AJ
University Chemical Laboratory, Cambridge CB2 1EW, UK. ajk1@cam.ac.uk
Camilleri
Patrick
P
Engberts
Jan B F N
JB
Feiters
Martin C
MC
Nolte
Roeland J M
RJ
Söderman
Olle
O
Bergsma
Mark
M
Bell
Paul C
PC
Fielden
Matthew L
ML
García Rodríguez
Cristina L
CL
Guédat
Philippe
P
Kremer
Andreas
A
McGregor
Caroline
C
Perrin
Christele
C
Ronsin
Gaël
G
van Eijk
Marcel C P
MC
D015316:Genetic Therapy / Q000379:methods*; D008081:Liposomes / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
D008081:Liposomes; D013501:Surface-Active Agents