초록 ▼

1. 보유한 비바이러스성 유전자 전달체의 개량
PAM-DET-deoxycholate를 합성하여 polyplex의 크기를 확인하였고 세포수준에서의 transfection test를 통해 PAM-DET와 PEI보다 transfection 효율이 향상된 것을 확인. 또한 PAM-chol 유도체 합성 방법을 정립하고 전달 효율과 세포 독성을 평가.
2. Amyloid beta pathology AD치료용 유전자 제작
Amyloid beta의 분해에 관여하는 단백질 스크리닝 후 재조합. 동물실험결과 therapeutic e

1. 보유한 비바이러스성 유전자 전달체의 개량
PAM-DET-deoxycholate를 합성하여 polyplex의 크기를 확인하였고 세포수준에서의 transfection test를 통해 PAM-DET와 PEI보다 transfection 효율이 향상된 것을 확인. 또한 PAM-chol 유도체 합성 방법을 정립하고 전달 효율과 세포 독성을 평가.
2. Amyloid beta pathology AD치료용 유전자 제작
Amyloid beta의 분해에 관여하는 단백질 스크리닝 후 재조합. 동물실험결과 therapeutic effect를 확인
3. siRNA 비강내 투여를 통한 gene knockdown 최적화 방안 개발
siRNA 비강투여에 있어 rat을 대상으로 protocol을 확립한 후 정상쥐에서 비강투여된 siRNA의 뇌조직 분포를 관찰한 결과 주입한 siRNA가 지속적으로 관찰됨. 또한 타겟단백질의 발현을 효과적으로 억제하는 것을 확인한 후 다른 조직으로의 변화를 조사. 또한 뇌졸중 동물모델에서도 치료효과 검증.

Abstract ▼

The purpose of the study is to develop a gene therapy technique using non viral gene delivery carriers for the treatment of brain tumor, stroke and ischemic diseases. The established technique is aimed to be efficient and safe enough for clinical trial by decreasing cytotoxicity, synthesizing effici

The purpose of the study is to develop a gene therapy technique using non viral gene delivery carriers for the treatment of brain tumor, stroke and ischemic diseases. The established technique is aimed to be efficient and safe enough for clinical trial by decreasing cytotoxicity, synthesizing efficient gene delivery carrier, and improving the structure of plasmid which contains a therapeutic gene. Besides injection as a means of treatment, intranasal delivery will also be carried out to enhance the efficacy of the siRNA delivery and to develop therapeutic strategy to alleviate brain damage by combined treatment which include gene therapy and other neuroprotective method.
Non-viral gene delivery carriers have advantages such as non-immunogenicity, convenient handling, and unlimited capacity for gene delivery in comparison with viral vector which have severe immunogenicity, the possibility of permanent insertion into the host genome, difficulties of handling, or limited capacity for gene delivery. This study focuses on the advancement and improvement of gene delivery carriers and their delivering capacity, to be appropriate for clinical application. Polymeric gene carriers with anti-inflammatory effect will be further developed. In addition, a delivery system for in vivo brain tumor treatment and a hypoxia specific gene expression system will be developed for localization of therapeutic gene in ischemic tissues. For more efficient alleviation of brain damage in the postischemic brain, experiments such as developing an effective strategy to deliver siRNA intranasally and knock down target gene in the brain, examining the protective effect of intranasally-delivered siRNA-based gene knockdown in stoke animal model, developing effective strategy for combination treatment of beneficial drug with siRNA of harmful gene and developing a therapeutic strategy to alleviate brain damage by combined treatment which include gene therapy and other methods, were carried out.