Oral gene therapy: a novel method for the manufacture and delivery of protein drugs.
Despite the great promise of a broadly based protein pharmaceutics, the use of protein drugs remains limited by drug availability due to the complexity and cost of manufacture, and patient compliance because of the need for needle injection. In this article we present proof of principle for a concept that avoids these difficulties and offers the prospect of greatly expanding the use and utility of protein drugs. Rather than the protein itself, the drug is a DNA plasmid that codes for it, that is swallowed, not injected. The protein is manufactured by the body in cells of the small intestine and is delivered by them into the bloodstream. The drug has a short-lived action and like other oral medications must be taken frequently (every day or two) to be effective. The short term of action is an advantage that provides for safe, easily managed treatment, unlike most gene-based therapies in use today. The dose of the drug can be altered from day to day, and treatment can be stopped quickly if untoward side effects are observed.
Rothman
Stephen
S
University of California, San Francisco, San Francisco, California 94708, USA. rothman@itsa.ucsf.edu
Tseng
Hsien
H
Goldfine
Ira
I
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004386:Duodenum; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007328:Insulin / Q000032:analysis / Q000235:genetics; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008297:Male; D051379:Mice; D023421:Models, Animal; D010957:Plasmids; D011506:Proteins / Q000008:administration & dosage / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D007328:Insulin; D011506:Proteins; D008156:Luciferases