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Related Concept Videos

Gene Therapy00:59

Gene Therapy

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Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be...
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Related Experiment Video

Updated: May 23, 2025

Dextran Enhances the Lentiviral Transduction Efficiency of Murine and Human Primary NK Cells
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Advancing Allogeneic NK Cell Immunotherapy through Microfluidic Gene Delivery.

Hyelee Kim1,2, Mujin Lee3, Bohwa Han3

  • 1Department of Bioengineering, Korea University, Seoul, 02841, Republic of Korea.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|March 7, 2025
PubMed
Summary
This summary is machine-generated.

A new microfluidic device, the Y-hydroporator, efficiently engineers chimeric antigen receptor (CAR)-natural killer (NK) cells for cancer immunotherapy. This technology enhances NK cell cytotoxicity while maintaining viability, paving the way for improved allogeneic immunotherapies.

Keywords:
CAR‐NKCRISPRNK cell‐based immunotherapyallogeneic cell therapygene deliverymicrofluidics

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Area of Science:

  • Biotechnology
  • Immunotherapy
  • Cell Engineering

Background:

  • Chimeric antigen receptor (CAR)-T cell therapy shows promise but faces manufacturing and safety challenges.
  • CAR-natural killer (NK) cell therapies offer an alternative with innate cytotoxicity and reduced safety risks.
  • Efficient genetic engineering and large-scale production of allogeneic NK cells are critical unmet needs.

Purpose of the Study:

  • To develop a novel microfluidic platform for efficient gene delivery to allogeneic NK cells.
  • To overcome manufacturing and engineering hurdles in CAR-NK cell immunotherapy.
  • To demonstrate the platform's capability in generating functional engineered NK cells.

Main Methods:

  • Development of the Y-hydroporator, a microfluidic device with a Y-shaped channel for hydrodynamic stretching of NK cells.
  • Utilizing the Y-hydroporator for delivering mRNA and CRISPR/Cas9 ribonucleoproteins to primary human NK cells.
  • Assessing cell viability, functionality, and transfection efficiency post-delivery.

Main Results:

  • The Y-hydroporator achieved high delivery and transfection efficiency (≈2 × 106 cells min-1) with high cell viability (>89%).
  • Successfully generated anti-CD19 CAR-NK cells and NKG2A-knockout NK cells.
  • Engineered NK cells exhibited enhanced cytotoxic activity against target cells.

Conclusions:

  • The Y-hydroporator is a highly efficient and viable platform for engineering allogeneic NK cells.
  • This technology has the potential to advance the development and application of NK cell-based immunotherapies.
  • The platform addresses key challenges in the manufacturing of CAR-NK cells for cancer treatment.