Dose-response and control of adeno-associated viral vectors based preclinical and clinical gene therapy / 中国临床药理学与治疗学

ABSTRACT

Human gene therapy needs to express exogenous DNA at the targeting cells,producing a practical and efficient therapeutic dosage at an approp-riate time(quantitative pharmacology)with a safe man-ner.Recombinant adeno-associated virus(rAAV)Vec-tom possess a number of properties and recent progress in rAAV production made it rapidly become the reagent of choice for therapeutic gene tmasfer.Over 60 clinical trials of gene therapy based on rAAV have been carried out.The dose response reaction between rAAV vectors and gene expression activity or clinical outcome is one of major aspects of these trials.Most studies showed that vector genomes(vg)and gene expression had a concentration-dependent relationship during a certain scope.However,gene expr~sion Can be afffected by viral serotypes,tissue tropisms,cell targeting,drug regulation,injection route,age and sex,etc.Thus,these aspects should be carefully comidered by scienti-sts,pharmacologisis and physicians during animal ex-periments or clinical trails.KEY WORDS gene therapy;viral vector;dose-re-sponse;quantitative pharmacology;clinical thempy