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Adv. Sci., 07 March 2025 | https://doi.org/10.1002/advs.202412544
Advancing Allogeneic NK Cell Immunotherapy through Microfluidic Gene Delivery
Hyelee Kim 1,2, Mujin Lee 3, Bohwa Han 3, Jinho Kim 4, Duck Cho 4,5, Junsang Doh 3, Aram J. Chung 1,2,6,7,*
1Department of Bioengineering Korea University Seoul 02841, Republic of Korea
2Interdisciplinary Program in Precision Public Health(PPH) Korea University Seoul 02841, Republic of Korea
3Department of Materials Science and Engineering Seoul National University Seoul 08826, Republic of Korea
3Department of Materials Science and Engineering Seoul National University Seoul 08826, Republic of Korea
4Department of Health Sciences and Technology SAIHST Sungkyunkwan University Seoul 06355, Republic of Korea
5Department of Laboratory Medicine and Genetics Samsung Medical Center Sungkyunkwan University School of Medicine Seoul 03063, Republic of Korea
6School of Biomedical Engineering Korea University Seoul 02841, Republic of Korea
7MxT Biotech Seoul 04785, Republic of Korea
*Corresponding author: correspondence to Aram J. Chung
Abstract
Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment, yet challenges such as manufacturing complexity, high costs, and safety concerns have spurred the development of alternatives like CAR-natural killer (NK) cell immunotherapies. CAR-NK cell therapies provide innate cytotoxicity with antigen-independent targeting, reducing safety risks while improving therapeutic efficacy. However, efficient genomic engineering and large-scale production of allogeneic NK cells remain significant obstacles. To address these challenges, a novel microfluidic gene delivery platform is developed, the Y-hydroporator, designed for allogeneic NK cell immunotherapy. This platform features a Y-shaped microchannel where NK cells experience rapid hydrodynamic stretching near the stagnation point, creating transient membrane discontinuities that facilitate the uptake of exogenous cargo. The Y-hydroporator achieves high delivery and transfection efficiency, processing ≈2 × 106 cells min−1 while maintaining long-term cell viability (>89%) and functionality. Using this platform, human primary CAR-NK cells and NKG2A-knockout NK cells are successfully generated by delivering anti-CD19 CAR mRNA and CRISPR/Cas9 ribonucleoproteins, respectively. These engineered NK cells demonstrated enhanced cytotoxicity, underscoring the potential of the Y-hydroporator as a transformative tool for advancing allogeneic NK cell-based immunotherapies.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-10)
- 국내 연구진
- 바이오·의료융합 > 다학제 융합/복합
관련 보도자료
NK세포 유전자 편집 플랫폼 연구성과 학술지 게재
엠엑스티 바이오텍은 고려대학교와 함께 유체천공기를 이용해 인간 일차 NK세포의 유전자 편집을 수행한 연구성과를 국제학술지 Advanced Science에 게재했다고 지난 12일 밝혔다. 연구 결과에 따르면, 유체천공기를 활용한 유전자 전달 프로세스 후 NK세포는 89% 이상 세포 생존율을 유지하면서도 90% 이상 유전자 전달 효율을 나타냈다. 또한, 유체천공기를 통한 형질 변환으로 제작한 CAR-NK 세포 및 CRISPR 기반 유전자 편집(NKG2A Knock-out) NK 세포에서도 암세포 살해 능력과 안전성이 확인됐다.
- 히트뉴스
- 2025. 03. 18
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