Kassim Sadik H, Wilson James M, Rader Daniel J
University of Pennsylvania School of Medicine, Gene Therapy Program, Department of Pathology & Laboratory Medicine, 125 South 31st Street (Suite 2000), PA 19104, USA.
Clin Lipidol. 2010 Jun;5(6):793-809. doi: 10.2217/clp.10.73.
Despite numerous technological and pharmacological advances and more detailed knowledge of molecular etiologies, cardiovascular diseases remain the leading cause of morbidity and mortality worldwide claiming over 17 million lives a year. Abnormalities in the synthesis, processing and catabolism of lipoprotein particles can result in severe hypercholesterolemia, hypertriglyceridemia or low HDL-C. Although a plethora of antidyslipidemic pharmacological agents are available, these drugs are relatively ineffective in many patients with Mendelian lipid disorders, indicating the need for new and more effective interventions. In vivo somatic gene therapy is one such intervention. This article summarizes current strategies being pursued for the development of clinical gene therapy for dyslipidemias that cannot effectively be treated with existing drugs.
尽管在技术和药理学方面取得了诸多进展，并且对分子病因有了更详细的了解，但心血管疾病仍然是全球发病和死亡的主要原因，每年夺去超过1700万人的生命。脂蛋白颗粒的合成、加工和分解代谢异常可导致严重的高胆固醇血症、高甘油三酯血症或低高密度脂蛋白胆固醇。虽然有大量的抗血脂异常药物可供使用，但这些药物对许多患有孟德尔脂质紊乱的患者相对无效，这表明需要新的、更有效的干预措施。体内体细胞基因治疗就是这样一种干预措施。本文总结了目前正在为开发现有药物无法有效治疗的血脂异常临床基因治疗所采用的策略。
