| 학회 | 한국재료학회 |
| 학술대회 | 2019년 가을 (10/30 ~ 11/01, 삼척 쏠비치 호텔&리조트) |
| 권호 | 25권 2호 |
| 발표분야 | 특별심포지엄9. 여성위원회 특별세션-오거나이저:윤희숙(KIMS) |
| 제목 | Application of cationic polymer as nucleic acid carrier into nerve tissue |
| 초록 | Physical trauma results in damage to the central nervous system (CNS). The regenerative capacity of the injured CNS is extremely limited, due to both extrinsic microenvironmental factors and intrinsic neuronal biochemistry. Neurite growth inhibitors such as MAIs and CSPGs have been shown to be associated with activation of RhoA and Rho kinase (ROCK) and can be overcome by Rho/ROCK inhibitors. The goal of our work is to develop multi-functional polymeric micelle for combinatorial delivery of multiple bioactive molecules targeting different barriers to plasticity and axonal regeneration. We designed copolymers (poly(lactide-co-glycolide)–g-polyethylenimine : PgP). We show that PgP micelle can achieve efficient knockdown of RhoA expression in the rat compression spinal cord injury model in vivo. After generation of SCI model, PgP/RhoAsiRNA polyplexes were injected into spinal cord injury site. In untreated SCI group, the relative RhoA mRNA level in spinal cord was significantly higher than that in sham group for up to 4 weeks post-injury. The relative RhoA mRNA level in both treatment groups (single injection and repeat injection) was significantly lower than that in untreated SCI animal group. We observed an extensive necrotic lesion cavity and significant reactive astrogliosis in the spinal cord from untreated SCI animal group, while reduced cavitation/astrogliosis and axonal regeneration into the lesion site in spinal cord from PgP/siRhoA polyplex-treated animal group was observed. These studies demonstrate that the cationic, amphiphilic copolymer PgP is a promising therapeutic siRNA delivery carrier in rat compression spinal cord injury model in vivo and knockdown Rho A for up to 4 weeks. RhoA knockdown by PgP/siRho A reduced apoptosis, cavitation and increased axson regeneration. These studies demonstrate that PgP is an efficient nucleic acid carrier for therapeutic RhoA siRNA to the spinal cord injury. |
| 저자 | So-Jung Gwak |
| 소속 | Department of Chemical Engineering |
| 키워드 | spinal cord injury; Rho A siRNA; gene delivery |
