Related Experiment Video
Updated: Aug 10, 2025
07:20
Generation of Knock-out Primary and Expanded Human NK Cells Using Cas9 Ribonucleoproteins
Published on: June 14, 2018
12.6K
Subpopulation Heterogeneity of NK Cells during the Genetic Modification for Subsequent Use in Targeted Therapy
M A Streltsova1, A A Boyko1, M O Ustiuzhanina1,2
1Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Doklady. Biochemistry and Biophysics
|February 14, 2023
Summary
Genetically engineered Natural Killer (NK) cells show promise in immunotherapy. This study found specific NK cell subsets, like those expressing KIR2DL2/DL3 and NKG2C, are more efficiently modified, developing an adaptive phenotype.
Area of Science:
- Immunotherapy and cellular engineering
- Immunology and NK cell biology
Background:
- Genetically engineered Natural Killer (NK) cells are a rapidly advancing field in immunotherapy.
- Understanding NK cell subset heterogeneity is crucial for optimizing genetic modification strategies.
Purpose of the Study:
- To analyze the subset heterogeneity of NK cells during retroviral transduction.
- To identify NK cell progenitors with adaptive characteristics and assess their susceptibility to genetic modification.
Main Methods:
- Retroviral transduction of NK cell subsets.
- Analysis of NK cell subset composition, including adaptive NK cell progenitors.
- Flow cytometry to assess cell surface marker expression (KIR2DL2/DL3, CD57, NKG2C) before and after genetic modification.
Main Results:
- NK cell subsets expressing KIR2DL2/DL3, and specifically CD57-KIR2DL2/DL3+NKG2C+ subsets, demonstrated higher transduction efficiency compared to subsets lacking these markers.
- Following genetic modification, CD57-KIR2DL2/DL3+NKG2C+ cells acquired de novo CD57 expression, indicating the development of an adaptive NK cell phenotype.
Conclusions:
- Specific KIR2DL2/DL3 and NKG2C expressing NK cell subsets are more amenable to genetic engineering via retroviral transduction.
- The observed de novo CD57 expression suggests a pathway for inducing an adaptive NK cell phenotype through genetic modification.
