초록

● microRNA library screening 을 통하여 EGFR mutation 폐암에서 최적의 효능을 갖는 miRNA 발굴
● miRNA 에 의한 폐암 apoptosis 작용 기전 규명
● miRNA 기반의 SAMiRNA 나노 입자 효능 평가
● orthotopic 폐암 동물 모델 제작
● 동물 모델에서의SAMiRNA 나노입자의 독성 및 효능 평가

(출처 : 보고서 요약서 3p)

Abstract ▼

Purpose&Contents
In order to develop an innovative medicine which inhibits signaling pathway critical for the survival of cancer, we screened miRNA library to identify potent miRNAs which led apoptosis of cancer cell lines, especially in non-small cell lung cancer (NSCLC), and revealed mechanism

Purpose&Contents
In order to develop an innovative medicine which inhibits signaling pathway critical for the survival of cancer, we screened miRNA library to identify potent miRNAs which led apoptosis of cancer cell lines, especially in non-small cell lung cancer (NSCLC), and revealed mechanism by which the cancer cells entered the apoptosis. The candidate miRNAs were loaded on SAMiRNA nano particle and tested for the efficacy in animal models. The purpose of the research was the discovery of candidate miRNA medicines for lung cancers.

Results
The research was performed to develop an efficacious medicine based on miRNAs to cure EGFR mutation lung cancers which had the resistance to Erlotinib and Gefitifnib. For this purpose, human miRNA library was produced which contains approximate 2000 human miRNAs known up to date and was subjected to screening process. Through the screening, several miRNAs were identified which inhibited the proliferation of cancer cells. We discovered that miRNAs inhibits the proliferation by inducing apoptosis of cells. In addition, miR-544a and miR-648 which were selected lead candidates for miRNA-based medicine were unveiled to block the EGFR signaling pathway by directly repressing the expression of EGFR protein. Of note, miR-544a was found to regulate the EGFR by binding the 3' UTR of the EGFR transcript at three different sites. When miR-544a or miR-648 was treated to cancer cell lines having the resistance to Erlotinib or Gefitinib, miRNAs were shown to induce the apoptosis effectively at low concentration of miRNAs.

The miRNAs in the form of SAMiRNAs were evaluated in animal models. The sense strand of SAMiRNA was modified to increase the structural stability. The new version of the SAMiRNA was tested in orthotopic or xenograft lung cancer animal model. SAMiRNA was proven to effectively suppress the tumor compared to non-treated group. In addtion, no toxic effect was detected at 30 mpk injection of SAMiRNA.

Expected Contribution
There was no precedent of miRNA-based medicine, but the supriority in terms of efficacy and safety would be expected to be proved. It is also expected to provide an alternative to develop medicines for the disease of no medicine, and to play pivotal roles in the newly created market.

The results of the research could be applied to other types of cancers having EGFR mutation, although the current research was carried out in lung cancer model. Therefore, it is highly expected to be utilized to develop anti-cancer drugs of other types of cancers, too.

(출처 : SUMMARY 5p)

목차 Contents

• 표지 ... 1
• 제 출 문 ... 2
• 보고서 요약서 ... 3
• 국문 요약문 ... 4
• SUMMARY ... 5
• Contents ... 6
• 목차 ... 7
• 1. 연구개발과제의 개요 ... 8
• 1-1. 연구개발 목적 ... 8
• 1-2. 연구개발의 필요성 ... 8
• 1-3. 연구개발 범위 ... 12
• 2. 국내외 기술개발 현황 ... 13
• 3. 연구수행 내용 및 결과 ... 27
• 4. 목표달성도 및 관련분야 기여도 ... 99
• 4-1. 목표달성도 ... 99
• 4-2. 관련분야 기여도 ... 101
• 5. 연구결과의 활용계획 ... 102
• 6. 연구과정에서 수집한 해외과학기술정보 ... 104
• 7. 연구개발성과의 보안등급 ... 115
• 8. 국가과학기술종합정보시스템에 등록한 연구시설·장비 현황 ... 115
• 9. 연구개발과제 수행에 따른 연구실 등의 안전조치 이행실적 ... 116
• 10. 연구개발과제의 대표적 연구실적 ... 117
• 11. 기타사항 ... 117
• 12. 참고문헌 ... 118
• [별첨4] 실적 증빙자료 ... 122
• 끝페이지 ... 124