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信号来确定性治疗软骨发育不全。使用非病毒基因载体polyplex nanomicelle将该基因导入野生型幼年小鼠，与对照小鼠相比，诱导了约2%的四肢骨延长的治疗效果。然而，在使用软骨发育不全模型小鼠的实验中，未观察到显著效果。为了寻求一种更有效的基因导入技术，研究了结合基因修饰的细胞球移植系统。皮下移植接受基因转染的球状体，使用纳米胶束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.