期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 20, 页码 10976-10982出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1917125117
关键词
acoustofluidics; hematopoietic stem cells; intracellular delivery; gene therapy
资金
- National Institute of Health [5P30 AI028697]
- NIH [U54HL119893, R01GM132603, R33CA223908, R01GM127714]
- NIH National Center for Advancing Translational Sciences (NCATS) UCLA Clinical and Translational Science Institute (CTSI) through the University of California (UC) Center for Accelerated Innovation [KL2TR001882, UL1TR001881]
- NIH
- National Heart, Lung, and Blood Institute of the NIH [F31HL149356]
- National Science Foundation [DGE-1144087]
- UCLA chemistry department
- American Italian Cancer Foundation
- National Cancer Institute (NCI) [K23CA222659]
- American Society of Hematology
- UCLA Innovation Fund MedTech Innovator Award
- UCLA David Geffen School of Medicine Regenerative Medicine Theme Award
- NIH Common Fund through a NIH Director's Early Independence Award - National Institute of Dental and Craniofacial Research
- Office of the Director, NIH [DP5OD028181]
- Alex's Lemonade Stand Foundation for Childhood Cancer Research
- Hyundai Hope on Wheels Foundation for Pediatric Cancer Research
- Tower Cancer Research Foundation
- European Hematology Association [TRTH30] Funding Source: researchfish
Advances in gene editing are leading to new medical interventions where patients' own cells are used for stem cell therapies and immunotherapies. One of the key limitations to translating these treatments to the clinic is the need for scalable technologies for engineering cells efficiently and safely. Toward this goal, microfluidic-strategies to induce membrane pores and permeability have emerged as promising techniques to deliver biomolecular cargo into cells. As these technologies continue to mature, there is a need to achieve efficient, safe, nontoxic, fast, and economical processing of clinically relevant cell types. We demonstrate an acoustofluidic sonoporation method to deliver plasmids to immortalized and primary human cell types, based on pore formation and permeabilization of cell membranes with acoustic waves. This acoustofluidic-mediated approach achieves fast and efficient intracellular delivery of an enhanced green fluorescent protein-expressing plasmid to cells at a scalable throughput of 200,000 cells/min in a single channel. Analyses of intracellular delivery and nuclear membrane rupture revealed mechanisms underlying acoustofluidic delivery and successful gene expression. Our studies show that acoustofluidic technologies are promising platforms for gene delivery and a useful tool for investigating membrane repair.
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