Gene therapy for achodroplasia using a biocompatible non-viral gene delivery system

本研究旨在通过使用CNP （c型利钠肽）表达基因调节FGFR3信号来确定软骨发育不全的治疗方法。利用一种非病毒基因载体，polyplex纳米胶束，将该基因引入野生型幼鼠体内，与对照小鼠相比，其四肢骨伸长率约为2%。然而，在软骨发育不全模型小鼠的实验中，没有观察到明显的影响。为寻求一种更有效的基因导入技术，研究了细胞球体移植与基因修饰相结合的系统。用纳米胶束进行基因转染的球体皮下移植在宿主小鼠中提供了高的连续转基因表达。我们计划在未来的研究中应用细胞移植系统治疗软骨发育不全。

This study is aiming at definitive therapy of achondroplasia by regulating FGFR3 signals using CNP (C-type natriuretic peptide)-expressing gene. Introducing the gene into wild-type infant mice using a non-viral gene carrier, polyplex nanomicelle, induced a therapeutic effect of bone elongation of the extremities at approximately 2 % compared with control mice. However, in experiments using model mice of achondroplasia, no significant effects were observed. Pursuing a more effective technique to introduce gene, cell spheroid transplantation system combined with genetic modification was investigated. Subcutaneous transplantation of spheroids that had received gene transfection using the nanomicelle provided high continuous transgene expression in host mice. We are planning to apply the cell transplantation system for treating achondroplasia in the future study.