Gastroprotection of DNA with a synthetic cholic acid analog.
The oral delivery of functional DNA to the gastrointestinal system would constitute a desirable, noninvasive method for potentially treating a variety of diseases. The digestive process, however, remains a formidable barrier. This dilemma may be addressed by using targeted liposomes both to protect the polynucleotide and to deliver the therapeutic DNA with high tissue specificity. The present study represents the initial steps toward developing a novel gene delivery system designed to interact with the enterohepatic receptors of the small intestine. Two cholic acid esters were synthetically modified at position C(3) to incorporate a DNA-binding domain. These novel compounds were evaluated for their ability to protect DNA from the nucleases found in gastrointestinal segments. Additionally, the compounds were screened as a component of a gene delivery vector. Formulations containing the new bile salt derivatives protected DNA from degradation for more than 2 h and were capable of transfecting cultured NIH 3T3 cells.
Niedzinski
E J
EJ
Department of Chemistry, University of California-Davis, 95616, USA.
Bennett
M J
MJ
Olson
D C
DC
Nantz
M H
MH
D016475:3T3 Cells; D000284:Administration, Oral; D000818:Animals; D002793:Cholic Acids / Q000138:chemical synthesis; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D004064:Digestive System; D004337:Drug Carriers; D005260:Female; D018014:Gene Transfer Techniques; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D013329:Structure-Activity Relationship; D014162:Transfection / Q000379:methods
D002793:Cholic Acids; D004337:Drug Carriers; D007202:Indicators and Reagents; D019382:Human Growth Hormone; D004247:DNA