PDF(Pubmed)
Abstract：
Inherited genetic disorders of the liver pose a significant public health burden. Liver transplantation is often limited by the availability of donor livers and the exorbitant costs of immunosuppressive therapy. To overcome these limitations, nucleic acid therapy provides a hopeful alternative that enables gene repair, gene supplementation, and gene silencing with suitable vectors. Though viral vectors are the most efficient and preferred for gene therapy, pre-existing immunity debilitating immune responses limit their use. As a potential alternative, lipid nanoparticle-mediated vectors are being explored to deliver multiple nucleic acid forms, including pDNA, mRNA, siRNA, and proteins. Herein, we discuss the broader applications of lipid nanoparticles, from protein replacement therapy to restoring the disease mechanism through nucleic acid delivery and gene editing, as well as multiple preclinical and clinical studies as a potential alternative to liver transplantation.
摘要：
肝脏的遗传性疾病构成了重大的公共卫生负担。肝移植通常受到供体肝脏的可用性和免疫抑制治疗的高昂成本的限制。为了克服这些限制,核酸治疗提供了一个有希望的替代方案，使基因修复，基因补充，用合适的载体进行基因沉默。虽然病毒载体是基因治疗最有效和首选的，预先存在的免疫衰弱的免疫反应限制了它们的使用。作为一种潜在的选择,脂质纳米颗粒介导的载体正在探索提供多种核酸形式，包括pDNA,mRNAsiRNA和蛋白质。在这里，我们讨论了脂质纳米粒的更广泛的应用，从蛋白质替代疗法到通过核酸递送和基因编辑恢复疾病机制，以及多项临床前和临床研究作为肝移植的潜在替代方案。
