Development of Microfluidic Chip for Genomic Editing
and Manipulation of Stem and Immune Cells
Various genetically modified materials may be delivered into cells
without using electric energy or a virus.
Substantial contributions to cell therapy research are expected.
Professor Chung A-ram’s group publishes their results
in the online edition of the internationally renowned journal, ACS Nano.
▲ Professor Chung A-ram (left); and Hur Jeong-soo (right, first author, researcher) of the School of Biomedical Engineering, Korea University.
Professor Chung A-ram’s group from the School of Biomedical Engineering, College of Health Science, developed a microfluidic chip for the genomic editing and manipulation of stem cells or immune cells. Their report was published in the online edition of the internationally renowned journal ACS Nano (If: 14.5) on October 9.
Unlike general cell lines, primary cells, such as stem cells or immune cells, have a limited lifetime, and their genes are very difficult to manipulate. Nevertheless, because the genomic editing of primary cells is necessary in the development of therapeutic cells, there has been a need for developing a technology that can effectively transform primary cells. In particular, recent cancer immunotherapy has successfully treated intractable cancers, including hematologic malignancies. There is now an urgent need for developing a genomic editing technology for a large amount of immune cells to commercialize the therapy and apply it to the treatment of solid cancers.
The microfluidic intracellular delivery platform developed by Professor Chung A-ram’s group is different from existing technologies because it is capable of delivering various genetically modified materials into cells by using only a fluid flow formed within microchannels without using electric energy or a virus. The versatility of the technology allows for the high-efficiency delivery of materials of various sizes regardless of cell type. In particular, with regard to stem cells (human umbilical cord-derived stem cells and lipid-derived stem cells) and immune cells (dendritic cells from mouse bone marrow), which are primary cells, the technology showed a higher transformation yield than commercial electroporation technology and polymer carrier-based technology. In addition, the technology can be used to transform a large amount of cells (over 1 million cells per minute), and thus is expected to make substantial contributions to studies on cell therapy.
▲ Figure 1. (A) Schematic of microfluidic channel-based intracellular delivery platform and cell membrane penetration process (i–iii).
(B) An image of the K562 cell into which a fluorescent material has been delivered.
While various nanoparticles are actively studied to edit cellular functions, the research group showed that nanoparticles having a diameter of up to 300 nm can be delivered into the cytoplasm by using this technology, which may provide a cornerstone on which future nanoparticle-based cellular engineering can build.
▲ Figure 2. (A) Comparison of primary cell genomic editing efficiency between the microfluidic intracellular delivery platform and conventional technologies. (B) Images of the control and the K562 cell into which a fluorescent material has been delivered.
Hur Jeong-soo, the first author of the article, said, “Intracellular delivery is an essential technology for various studies in biotechnology.” He also explained the significance of the study: “For the first time in the world, we successfully transformed the DNA of stem cells by using only the flow within microchannels, and the efficiency of the primary cell genomic editing was higher than that of the existing, commercially available technologies.”
The present study was supported by the Samsung Research Funding and Incubation Center for Future Technology, Korea University, and the National Research Foundation of Korea
*Title of article: Microfluidic Cell Stretching for Highly Effective Gene Delivery into Hard-to-Transfect Primary Cells
*Authors: Hur Jeong-soo (Korea University, first author), Park In-ae (POSTEC), Lim Kyung-min (Konkuk University), Doh Junsang (Seoul National University), Cho Ssang-goo (Konkuk University) and Chung A-ram (Korea University, corresponding author)(https://pubs.acs.org/doi/10.1021/acsnano.0c05169)