한빛사논문, 상위피인용논문
- 조회1,080
Yusook Chung1,2, Yongku Ryu1, Byung Chull An1, Yeo-Sang Yoon1, Oksik Choi1, Tai Yeub Kim1, Jaekyung Yoon2, Jun Young Ahn1, Ho Jin Park1, Soon-Kyeong Kwon2,3, Jihyun F. Kim2,* and Myung Jun Chung1,*
1R&D Center, Cell Biotech, Co., Ltd., 50 Aegibong-ro 409beon-gil, Gaegok-ri, Wolgot-myeon, Gimpo-si, Gyeonggi-do 10003, Republic of Korea.
2Department of Systems Biology, Division of Life Sciences, and Institute for Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.
3Division of Applied Life Science (BK21), Gyeongsang National University, 501 Jinju-daero, Jinju-si, Gyeongsangnam-do 52828, Republic of Korea.
*Correspondence
Abstract
Background
Successful chemoprevention or chemotherapy is achieved through targeted delivery of prophylactic agents during initial phases of carcinogenesis or therapeutic agents to malignant tumors. Bacteria can be used as anticancer agents, but efforts to utilize attenuated pathogenic bacteria suffer from the risk of toxicity or infection. Lactic acid bacteria are safe to eat and often confer health benefits, making them ideal candidates for live vehicles engineered to deliver anticancer drugs.
Results
In this study, we developed an effective bacterial drug delivery system for colorectal cancer (CRC) therapy using the lactic acid bacterium Pediococcus pentosaceus. It is equipped with dual gene cassettes driven by a strong inducible promoter that encode the therapeutic protein P8 fused to a secretion signal peptide and a complementation system. In an inducible CRC cell-derived xenograft mouse model, our synthetic probiotic significantly reduced tumor volume and inhibited tumor growth relative to the control. Mice with colitis-associated CRC induced by azoxymethane and dextran sodium sulfate exhibited polyp regression and recovered taxonomic diversity when the engineered bacterium was orally administered. Further, the synthetic probiotic modulated gut microbiota and alleviated the chemically induced dysbiosis. Correlation analysis demonstrated that specific bacterial taxa potentially associated with eubiosis or dysbiosis, such as Akkermansia or Turicibacter, have positive or negative relationships with other microbial members.
Conclusions
Taken together, our work illustrates that an effective and stable synthetic probiotic composed of P. pentosaceus and the P8 therapeutic protein can reduce CRC and contribute to rebiosis, and the validity and feasibility of cell-based designer biopharmaceuticals for both treating CRC and ameliorating impaired microbiota.
논문정보
- Research article
- 2021년 05월 (BRIC 등록일 2021-06-02)
- 국내 연구진
- 생명과학 > 분자생물학
- 60회 이상 인용된 논문
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