Andrews Chasity D, Luo Yang, Sun Ming, Yu Jian, Goff Arthur J, Glass Pamela J, Padte Neal N, Huang Yaoxing, Ho David D
Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
Mol Ther Methods Clin Dev. 2017 Sep 20;7:74-82. doi: 10.1016/j.omtm.2017.09.003. eCollection 2017 Dec 15.
Monoclonal antibodies (mAbs) have wide clinical utility, but global access is limited by high costs and impracticalities associated with repeated passive administration. Here, we describe an optimized electroporation-based DNA gene transfer platform technology that can be utilized for production of functional mAbs in vivo, with the potential to reduce costs and administration burdens. We demonstrate that multiple mAbs can be simultaneously expressed at protective concentrations for a protracted period of time using DNA doses and electroporation conditions that are feasible clinically. The expressed mAbs could also protect mice against lethal influenza or Ebola virus challenges. Our findings suggest that this DNA gene transfer platform technology could be a game-changing advance that expands access to effective mAb therapeutics globally.
单克隆抗体(mAb)具有广泛的临床应用价值,但由于成本高昂以及与重复被动给药相关的不便利性,其全球可及性受到限制。在此,我们描述了一种基于电穿孔的优化DNA基因转移平台技术,该技术可用于在体内产生功能性单克隆抗体,具有降低成本和给药负担的潜力。我们证明,使用临床上可行的DNA剂量和电穿孔条件,多种单克隆抗体能够在一段较长时间内以保护性浓度同时表达。所表达的单克隆抗体还能够保护小鼠免受致命性流感或埃博拉病毒的攻击。我们的研究结果表明,这种DNA基因转移平台技术可能是一项改变游戏规则的进展,有望在全球范围内扩大有效单克隆抗体疗法的可及性。