Abstract
Meganucleases are sequence-specific endonucleases recognizing large ( > 12 bp) sequence sites and several laboratories have used these proteins to induce highly efficient gene targeting in mammalian cells. The recent development of artificial endonucleases with tailored specificities has opened the door for a wide range of new applications, including therapeutic ones: redesigned endonucleases cleaving chosen sequences could be used to in gene therapy to correct mutated genes or introduce transgenes in chosen loci. Such “targeted” approaches markedly differ from current gene therapy strategies based on the random insertion of a complementing virus-borne transgene. As a consequence, they should bypass the odds of random insertion. Artificial fusion proteins including Zinc-Finger binding domains have provided important proofs of concept, however the toxicity of these proteins is still an issue. Today custom-designed homing endonucleases, the natural meganucleases, could represent an efficient alternative. After a brief description of the origin of the technology, current systems based on redesigned endonucleases will be presented, with a special emphasis on the recent advances in homing endonuclease engineering. Finally, we will discuss the main issues that will need to be addressed in order to bring this promising technology to the patient.
Keywords: I-SceI, I-CreI, ZFNs, homing endonucleases, gene correction, gene insertion, protein engineering, genome engineering, gene therapy, genome surgery
Current Gene Therapy
Title: Meganucleases and DNA Double-Strand Break-Induced Recombination: Perspectives for Gene Therapy
Volume: 7 Issue: 1
Author(s): Frederic Paques and Philippe Duchateau
Affiliation:
Keywords: I-SceI, I-CreI, ZFNs, homing endonucleases, gene correction, gene insertion, protein engineering, genome engineering, gene therapy, genome surgery
Abstract: Meganucleases are sequence-specific endonucleases recognizing large ( > 12 bp) sequence sites and several laboratories have used these proteins to induce highly efficient gene targeting in mammalian cells. The recent development of artificial endonucleases with tailored specificities has opened the door for a wide range of new applications, including therapeutic ones: redesigned endonucleases cleaving chosen sequences could be used to in gene therapy to correct mutated genes or introduce transgenes in chosen loci. Such “targeted” approaches markedly differ from current gene therapy strategies based on the random insertion of a complementing virus-borne transgene. As a consequence, they should bypass the odds of random insertion. Artificial fusion proteins including Zinc-Finger binding domains have provided important proofs of concept, however the toxicity of these proteins is still an issue. Today custom-designed homing endonucleases, the natural meganucleases, could represent an efficient alternative. After a brief description of the origin of the technology, current systems based on redesigned endonucleases will be presented, with a special emphasis on the recent advances in homing endonuclease engineering. Finally, we will discuss the main issues that will need to be addressed in order to bring this promising technology to the patient.
Export Options
About this article
Cite this article as:
Paques Frederic and Duchateau Philippe, Meganucleases and DNA Double-Strand Break-Induced Recombination: Perspectives for Gene Therapy, Current Gene Therapy 2007; 7 (1) . https://dx.doi.org/10.2174/156652307779940216
DOI https://dx.doi.org/10.2174/156652307779940216 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Non-Small Cell Lung Carcinoma: An Overview on Targeted Therapy
Current Drug Targets Resveratrol Enhances UVA-Induced DNA Damage in HaCaT Human Keratinocytes
Medicinal Chemistry On the Origin of Epidermal Cancers
Current Molecular Medicine Association of EGF rs4444903 and XPD rs13181 Polymorphisms with Cutaneous Melanoma in Caucasians
Medicinal Chemistry Hemangiomas, Angiosarcomas, and Vascular Malformations Represent the Signaling Abnormalities of Pathogenic Angiogenesis
Current Molecular Medicine Anthracyclines Still Prove Effective in Anticancer Therapy
Mini-Reviews in Medicinal Chemistry Hepatocyte Growth Factor Signaling in Cancer Metastasis
Current Signal Transduction Therapy Role of Immunostimulatory Molecules in Poultry Vaccines
Recent Patents on Biotechnology The Chemistry and Biology of the Bryostatins: Potential PKC Inhibitors in Clinical Development
Current Medicinal Chemistry Exploring the Role of Phytochemicals as Potent Natural Photosensitizers in Photodynamic Therapy
Anti-Cancer Agents in Medicinal Chemistry Molecular Imaging of Therapeutic Potential of Reporter Probes
Current Drug Targets Recent Advances in Small Molecule Inhibitors of VEGFR and EGFR Signaling Pathways
Current Topics in Medicinal Chemistry Should the Status of the Pathway Mediated by BRCA1 and BRCA2 be Evaluated Before Selecting Cancer Chemotherapy Drugs?
Current Pharmacogenomics The Potential Role of Pharmacogenomic and Genomic in the Adjuvant Treatment of Early Stage Non Small Cell Lung Cancer
Current Genomics Recent Advance in Polymer Based Microspheric Systems for Controlled Protein and Peptide Delivery
Current Medicinal Chemistry Targeting the Programmed Cell Death-1 Pathway in Genitourinary Tumors: Current Progress and Future Perspectives
Current Drug Metabolism Hypertension and Angiogenesis
Current Pharmaceutical Design Redistribution of CD95 into the Lipid Rafts to Treat Cancer Cells?
Recent Patents on Anti-Cancer Drug Discovery Patent Selections:
Recent Patents on Inflammation & Allergy Drug Discovery Studies on Anticancer Activities of Lactoferrin and Lactoferricin
Current Protein & Peptide Science