The Gene Pill and its therapeutic applications.
Gene delivery represents a revolutionary therapeutic approach with the potential for sustained protein production by the human body, leading to a convenient and effective method for systemic delivery of protein drugs. In this review, advantages of an orally administered DNA formulation, Gene Pill, are presented. Unlike previously described DNA delivery approaches, the Gene Pill enables DNA delivery in a non-invasive manner, leading to the secretion of therapeutic proteins into a patient's blood, supplanting the need for injection of therapeutic protein products. The Gene Pill also has potential for the development of oral DNA vaccination through expression of protein antigens in the gut lymphoid tissue. This approach limits the biodistribution of the delivered DNA to the gut and retains all of the safety advantages of non-viral gene delivery, including repeat dosing. Development of an oral DNA formulation involves overcoming several challenges, including depurination by low pH in the stomach, enzymatic degradation by DNases in the gut, crossing the physical barrier imposed by the mucus layer, cell entry, intracellular trafficking and nuclear uptake. The advantages of the Gene Pill technology, as well as challenges for its development, are presented in this review.
D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D015507:Drugs, Investigational / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism
D015507:Drugs, Investigational; D019444:Vaccines, DNA; D004247:DNA