ArticleMolecular therapy. Methods & clinical development2015
Efficient genome editing in hematopoietic stem cells with helper-dependent Ad5/35 vectors expressing site-specific endonucleases under microRNA regulation.
Article in Molecular therapy. Methods & clinical development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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The trial behind it
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Who cites it
38 citing papers in PubMed, 59 citations in OpenAlex.
- Drug delivery systems for CRISPR-based genome editors.Nature reviews. Drug discovery · 2023Review
- Article
- Review
- In vivo base editing by a single i.v. vector injection for treatment of hemoglobinopathies.JCI insight · 2022Article
- Engineered Zinc Finger Protein Targeting 2LTR Inhibits HIV Integration in Hematopoietic Stem and Progenitor Cell-Derived Macrophages: In Vitro Study.International journal of molecular sciences · 2022Article
- Understanding and overcoming adverse consequences of genome editing on hematopoietic stem and progenitor cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- Review
- Review
- 2LTRZFP Interacts Specifically to HIV-1 DNA without Off-Target Effects as Determined by Biolayer Interferometry.Biosensors · 2021Article
- In vivo HSPC gene therapy with base editors allows for efficient reactivation of fetal γ-globin in β-YAC mice.Blood advances · 2021Article
- In Vivo HSC Gene Therapy Using a Bi-modular HDAd5/35++ Vector Cures Sickle Cell Disease in a Mouse Model.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Advances and Obstacles in Homology-Mediated Gene Editing of Hematopoietic Stem Cells.Journal of clinical medicine · 2021Review
- High-Capacity Adenoviral Vectors: Expanding the Scope of Gene Therapy.International journal of molecular sciences · 2020Review
- Review
- Targeted Integration and High-Level Transgene Expression in AAVS1 Transgenic Mice after In Vivo HSC Transduction with HDAd5/35++ Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Adenovirus vectors in hematopoietic stem cell genome editing.FEBS letters · 2019Review
- Production of CRISPR/Cas9-Mediated Self-Cleaving Helper-Dependent Adenoviruses.Molecular therapy. Methods & clinical development · 2019Article
- Gene Therapy Approaches to Functional Cure and Protection of Hematopoietic Potential in HIV Infection.Pharmaceutics · 2019Review
- Gene Therapy Leaves a Vicious Cycle.Frontiers in oncology · 2019Review
- One-Vector System for Multiplexed CRISPR/Cas9 against Hepatitis B Virus cccDNA Utilizing High-Capacity Adenoviral Vectors.Molecular therapy. Nucleic acids · 2018Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
Genome editing with site-specific endonucleases has implications for basic biomedical research as well as for gene therapy. We generated helper-dependent, capsid-modified adenovirus (HD-Ad5/35) vectors for zinc-finger nuclease (ZFN)- or transcription activator-like effector nuclease (TALEN)-mediated genome editing in human CD34+ hematopoietic stem cells (HSCs) from mobilized adult donors. The production of these vectors required that ZFN and TALEN expression in HD-Ad5/35 producer 293-Cre cells was suppressed. To do this, we developed a microRNA (miRNA)-based system for regulation of gene expression based on miRNA expression profiling of 293-Cre and CD34+ cells. Using miR-183-5p and miR-218-5p based regulation of transgene gene expression, we first produced an HD-Ad5/35 vector expressing a ZFN specific to the HIV coreceptor gene ccr5. We demonstrated that HD-Ad5/35.ZFNmiR vector conferred ccr5 knock out in primitive HSC (i.e., long-term culture initiating cells and NOD/SCID repopulating cells). The ccr5 gene disruption frequency achieved in engrafted HSCs found in the bone marrow of transplanted mice is clinically relevant for HIV therapy considering that these cells can give rise to multiple lineages, including all the lineages that represent targets and reservoirs for HIV. We produced a second HD-Ad5/35 vector expressing a TALEN targeting the DNase hypersensitivity region 2 (HS2) within the globin locus control region. This vector has potential for targeted gene correction in hemoglobinopathies. The miRNA regulated HD-Ad5/35 vector platform for expression of site-specific endonucleases has numerous advantages over currently used vectors as a tool for genome engineering of HSCs for therapeutic purposes.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.