초록

간암치료 혁신 신약 개발을 위한 STAT3-SAMiRNA 후보물질 발굴 및 효능/독성 평가 연구. 간암 중개연구시스템 확립을 위한 간암환자 유래 세포배양법, PDX모델 개발, 유전체분석, 데이터베이스 구축등을 본 연구를 통하여 완료함

(출처 : 보고서 요약서 3p)

Abstract ▼

Purpose&Contents
[Purpose] Development of novel STAT3 inhibitors for HCC
[SAMiRNA-STAT3 efficacy and toxicology studies]
o Chemical modification studies to improve serum stability of SAMiRNA
o STAT3 target gene knockdown (KD) and anti-proliferation assay in human HCC cell line
o Mouse

Purpose&Contents
[Purpose] Development of novel STAT3 inhibitors for HCC
[SAMiRNA-STAT3 efficacy and toxicology studies]
o Chemical modification studies to improve serum stability of SAMiRNA
o STAT3 target gene knockdown (KD) and anti-proliferation assay in human HCC cell line
o Mouse IV PK study & Genetic toxicity (AMES test) and hERG assay

[Establishment of international hepatocellular carcinoma (HCC) translational research platform for precision medicine and drug discovery]
o Development of cell culture method for HCC patient-derived tissues
o Establishment of HCC tissue libraries and PDX model
o Establishment of genetic information database in HCC through genetic analysis of HCC patient tissues

Results
[SAMiRNA-STAT3 efficacy and toxicology studies]
o Improvement of SAMiRNA-STAT3 stability and STAT3 KD efficacy in serum condition using 2' OME and phosphorothioate chemical modification

o Determination of maximmal efficacy as 70% of STAT3 KD and 30% inhibition of human HCC cell line, respectively

o Determination of comparable in vivo efficacy of STAT3-SAMiRNA with sorafenib in Hep3B orthotopic xenograft model

o Definition of IV PK profile in mice and demonstration of low cardiac and genotoxic risk through AMES test and hERG assay

[Establishment of international HCC translational research platform for precision medicine and drug discovery]

o Optimization of HCC patient derived cell (PDC) culture and establishment of 3D organoid culture method

o Collecting 231 liver tissue libraries and establishment of several strains of PDX models
o Genetic analysis in 51 HCC patient tissues putting into database
o Screening of drug response in PDC using 70 drugs and establishment of drug-response heatmap for 40 drugs

Expected Contribution
o Establishment of patient-derived HCC drug discovery platform in association with Asian HCC translational research collaboration

o Applying translational research platform to discover best-matching drug based on patient's genetic information and improving patient's survival as well as quality of life

o Acceleration of preclinical/clinical studies of STAT3-SAMiRNA using international HCC translational research networks and commercialization of STAT3-SAMiRNA in domestic as well as global market

(출처 : SUMMARY 5p)

목차 Contents

• 표지 ... 1
• 제 출 문 ... 2
• 보고서 요약서 ... 3
• 국문 요약문 ... 4
• SUMMARY ... 5
• 목차 ... 6
• 1. 연구개발과제의 개요 ... 7
• 1-1. 연구개발 목적 ... 7
• 1-2. 연구개발의 필요성 ... 7
• 1-3. 연구개발 범위 ... 10
• 2. 국내외 기술개발 현황 ... 11
• 3. 연구수행 내용 및 결과 ... 12
• 3-1. 위탁과제 연구 수행 내용 및 결과 ... 24
• 4. 목표달성도 및 관련분야 기여도 ... 48
• 4-1. 목표 달성도 ... 48
• 4-2. 관련분야 기여도 ... 48
• 5. 연구결과의 활용계획 ... 49
• 6. 연구과정에서 수집한 해외과학기술정보 ... 50
• 7. 연구개발성과의 보안등급 ... 50
• 8. 국가과학기술종합정보시스템에 등록한 연구시설·장비 현황 ... 51
• 9. 연구개발과제 수행에 따른 연구실 등의 안전조치 이행실적 ... 51
• 10. 연구개발과제의 대표적 연구실적 ... 51
• 11. 기타사항 ... 51
• [별첨4] 실적 증빙자료 ... 52
• 끝페이지 ... 53