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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: Aug 18, 2025

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
06:10

Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates

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Multiplexed engineering and precision gene editing in cellular immunotherapy.

Alexander Biederstädt1,2, Gohar Shahwar Manzar3, May Daher1

  • 1Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.

Frontiers in Immunology
|December 9, 2022
PubMed
Summary
This summary is machine-generated.

Cellular immunotherapies show promise for cancer treatment, but challenges like limited persistence and tumor escape persist. Precision genome editing offers new tools to engineer more effective and safer cancer therapies.

Keywords:
CAR (chimeric antigen receptor)CRISPR screeningcell engineeringcell therapygene editingimmune effector cell

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Area of Science:

  • Oncology
  • Immunology
  • Genetics

Background:

  • Cellular immunotherapy, including CAR-T and TCR therapies, has revolutionized cancer treatment, offering long-term remission for some patients.
  • Despite successes, challenges such as limited *in vivo* persistence, immune cell exhaustion, tumor immune escape, and on-target off-tumor toxicities hinder efficacy.
  • Precision genome editing tools provide advanced strategies to overcome these limitations in engineered immune cells.

Purpose of the Study:

  • To review the co-evolution of cellular immunotherapy and precision genome editing for enhanced anti-cancer treatments.
  • To discuss engineering strategies, including nuclease-dependent and -independent genome editing, for developing more potent cellular therapeutics.
  • To explore the potential of multiplexed-engineered and gene-edited cell products in transforming cancer treatment paradigms.

Main Methods:

  • Review of current literature on cellular immunotherapy and precision genome editing techniques.
  • Analysis of nuclease-based (CRISPR/Cas9, TALEN) and nuclease-inactive (base, prime editors) genome editing platforms.
  • Discussion of engineering strategies to enhance immune cell functionality and overcome tumor microenvironment challenges.

Main Results:

  • Cellular immunotherapies have demonstrated significant clinical responses but face limitations in persistence and specificity.
  • Precision genome editing, particularly nuclease-inactive editors, offers safer genetic modification of immune cells without double-strand breaks.
  • Multiplexed engineering and gene editing hold potential for creating next-generation cellular therapeutics with improved anti-cancer activity.

Conclusions:

  • The integration of precision genome editing with cellular immunotherapy is expanding the possibilities for personalized cancer treatment.
  • Advanced gene editing tools are crucial for addressing current limitations and developing more robust cellular therapeutics.
  • Future developments in multiplexed-engineered and gene-edited cell products are expected to significantly advance cancer treatment strategies.