Animal models for target diseases in gene therapy--using DNA and siRNA delivery strategies.
Nanoparticles, including lipopolyamines leading to lipoplexes, liposomes, and polyplexes are targeted drug carrier systems in the current search for a successful delivery system for polynucleic acids. This review is focused on the impact of gene and siRNA delivery for studies of efficacy, pharmacodynamics, and pharmacokinetics within the setting of the wide variety of in vivo animal models now used. This critical appraisal of the recent literature sets out the different models that are currently being investigated to bridge from studies in cell lines through towards clinical reality. Whilst many scientists will be familiar with rodent (murine, fecine, cricetine, and musteline) models, few probably think of fish as a clinically relevant animal model, but zebrafish, madake, and rainbow trout are all being used. Larger animal models include rabbit, cat, dog, and cow. Pig is used both for the prevention of foot-and-mouth disease and human diseases, sheep is a model for corneal transplantation, and the horse naturally develops arthritis. Non-human primate models (macaque, common marmoset, owl monkey) are used for preclinical gene vector safety and efficacy trials to bridge the gap prior to clinical studies. We aim for the safe development of clinically effective delivery systems for DNA and RNAi technologies.
Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, UK. prsisb@bath.ac.uk
Ian S
IS
Blagbrough
Chiara
C
Zara
D000818:Animals; D002415:Cats; D002417:Cattle; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004195:Disease Models, Animal; D004285:Dogs; D016503:Drug Delivery Systems; D005260:Female; D005399:Fishes; D015316:Genetic Therapy / Q000941:ethics / Q000639:trends*; D006736:Horses; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011323:Primates; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D012756:Sheep; D013552:Swine
D034741:RNA, Small Interfering; D004247:DNA