TY - JOUR
T1 - Animal Models for Target Diseases in Gene Therapy - using DNA and siRNA Delivery Strategies
AU - Blagbrough, Ian S
AU - Zara, C
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - gene delivery
KW - pharmacodynamics
KW - efficacy
KW - RNAi
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=57749169059&partnerID=8YFLogxK
UR - http://dx.doi.org/10.1007/s11095-008-9646-8
U2 - 10.1007/s11095-008-9646-8
DO - 10.1007/s11095-008-9646-8
M3 - Article
SN - 0724-8741
VL - 26
SP - 1
EP - 18
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 1
ER -