Qiu P, Ziegelhoffer P, Sun J, Yang N S
Department of Cancer Gene Therapy, Agracetus Inc, Middleton, WI 53562, USA.
Gene Ther. 1996 Mar;3(3):262-8.
The use of mRNA to transfer genetic information into mammalian somatic cells in vivo or ex vivo may be advantageous in a number of gene therapy protocols. Success in utilizing in vivo RNA delivery for transgene expression has been extremely limited, partially due to RNA instability and to the lack of an efficient intracellular delivery mechanism applicable to a wide variety of tissue or organ systems. We report here that a particle-mediated gene delivery technology can be used to effectively deliver RNA molecules into a number of mammalian somatic tissue types. Expression from RNA transcripts of three reporter genes, firefly luciferase, human growth hormone and human alpha-1 antitrypsin, was detected in monolayer and suspension cell cultures bombarded in vitro, and in in vivo bombarded rat liver tissues, and mouse liver and epidermal tissues. Gene gun treatment of mouse epidermis in vivo with human alpha-1 antitrypsin messenger RNA elicited a strong, consistent antibody response which showed an increased titer with subsequent boosts. Results from this study point to future opportunities of applying RNA delivery techniques for transgenic studies, genetic vaccination, and gene therapy.
在许多基因治疗方案中，使用信使核糖核酸（mRNA）在体内或体外将遗传信息转移到哺乳动物体细胞中可能具有优势。在体内利用RNA递送实现转基因表达的成功案例极为有限，部分原因是RNA的不稳定性以及缺乏适用于多种组织或器官系统的高效细胞内递送机制。我们在此报告，一种粒子介导的基因递送技术可用于有效地将RNA分子递送至多种哺乳动物体细胞组织类型中。在体外轰击的单层和悬浮细胞培养物中，以及在体内轰击的大鼠肝脏组织、小鼠肝脏和表皮组织中，均检测到了三种报告基因（萤火虫荧光素酶、人生长激素和人α-1抗胰蛋白酶）的RNA转录本的表达。用人类α-1抗胰蛋白酶信使核糖核酸对小鼠表皮进行体内基因枪处理引发了强烈、持续的抗体反应，且随着后续加强免疫，抗体滴度升高。本研究结果为将RNA递送技术应用于转基因研究、基因疫苗接种和基因治疗指明了未来的机会。
