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Cited by 35CRISPR and Genetic EngineeringVirus-based gene therapy researchCAR-T cell therapy research

Homology-directed gene-editing approaches for hematopoietic stem and progenitor cell gene therapy

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Azhagiri, Manoj Kumar K., Babu, Prathibha, Venkatesan, Vigneshwaran, Thangavel, Saravanabhavan·2021·Stem Cell Research & Therapy
DOI 10.1186/s13287-021-02565-6PMC PMC8428126
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Abstract

The advent of next-generation genome engineering tools like CRISPR-Cas9 has transformed the field of gene therapy, rendering targeted treatment for several incurable diseases. Hematopoietic stem and progenitor cells (HSPCs) continue to be the ideal target cells for gene manipulation due to their long-term repopulation potential. Among the gene manipulation strategies such as lentiviral gene augmentation, non-homologous end joining (NHEJ)-mediated gene editing, base editing and prime editing, only the homology-directed repair (HDR)-mediated gene editing provides the option of inserting a large transgene under its endogenous promoter or any desired locus. In addition, HDR-mediated gene editing can be applied for the gene knock-out, correction of point mutations and introduction of beneficial mutations. HSPC gene therapy studies involving lentiviral vectors and NHEJ-based gene-editing studies have exhibited substantial clinical progress. However, studies involving HDR-mediated HSPC gene editing have not yet progressed to the clinical testing. This suggests the existence of unique challenges in exploiting HDR pathway for HSPC gene therapy. Our review summarizes the mechanism, recent progresses, challenges, and the scope of HDR-based gene editing for the HSPC gene therapy.

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  • An HDR enhancer and NHEJ inhibitor were used to improve homology-directed repair and efficient genome editing, particularly for precise single-nucleotide modifications.

    “An HDR enhancer and NHEJ inhibitor were used to improve homology-directed repair and efficient genome editing, particularly for precise single-nucleotide modifications (Figure 4A) [45,46].”

    From Precise CRISPR/Cas9 and Cas12 Correction Using Lipoplexes in Retinal Models Derived from Patients with Inherited Retinal Dystrophies (2026) · cites this paper as [45]

    The ‘Inhibition of competitive NHEJ pathway’ section reports that NHEJ inhibitors improve HDR and that a mixture including HDR-promoting molecules increased HDR in iPSCs. The ‘HDR gene editing’ section says HDR templates are tested for single-nucleotide changes. The paper does not establish that this enhancer–inhibitor approach was used particularly to improve precise single-nucleotide modifications. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Azhagiri, M. K. K., Babu, P., Venkatesan, V., & Thangavel, S.
Affiliations
  • Manipal Academy of Higher Education (IN)
  • Christian Medical College, Vellore (IN)
Corresponding author
Thangavel, Saravanabhavan
ORCID
Venue
Stem Cell Research & Therapy
Publisher
Springer Science and Business Media LLC
Published
2021-09-09
Volume
12
Issue
1
Pages
500-500
ISSN
1757-6512 (ISSN-L)
DOI
10.1186/s13287-021-02565-6
PMC
PMC8428126
OpenAlex
W3198155108
Cited by
35
References
9
Citations by year
2026: 5 · 2025: 7 · 2024: 10 · 2023: 8 · 2022: 4 · 2021: 1
FWCI
0.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Department of Biotechnology , Ministry of Science and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
Keywords
homology-directed repair, hematopoietic stem and progenitor cells, gene therapy, CRISPR/Cas9, lentiviral vectors, non-homologous end joining, base editing, prime editing, transgene integration, gene knockout, point mutation correction, hematopoietic stem cell transplantation
MeSH terms
Gene Editing, Hematopoietic Stem Cells, Genetic Therapy, Hematopoietic Stem Cell Transplantation, CRISPR-Cas Systems

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