Molecular Therapy: Nucleic Acids (Mar 2025)
Advanced delivery systems for gene editing: A comprehensive review from the GenE-HumDi COST Action Working Group
- Alessia Cavazza,
- Francisco J. Molina-Estévez,
- Álvaro Plaza Reyes,
- Victor Ronco,
- Asma Naseem,
- Špela Malenšek,
- Peter Pečan,
- Annalisa Santini,
- Paula Heredia,
- Araceli Aguilar-González,
- Houria Boulaiz,
- Qianqian Ni,
- Marina Cortijo-Gutierrez,
- Kristina Pavlovic,
- Inmaculada Herrera,
- Berta de la Cerda,
- Emilio M. Garcia-Tenorio,
- Eva Richard,
- Sergio Granados-Principal,
- Arístides López-Márquez,
- Mariana Köber,
- Marijana Stojanovic,
- Melita Vidaković,
- Irene Santos-Garcia,
- Lorea Blázquez,
- Emily Haughton,
- Dongnan Yan,
- Rosario María Sánchez-Martín,
- Loubna Mazini,
- Gloria Gonzalez Aseguinolaza,
- Annarita Miccio,
- Paula Rio,
- Lourdes R. Desviat,
- Manuel A.F.V. Gonçalves,
- Ling Peng,
- Cecilia Jiménez-Mallebrera,
- Francisco Martin Molina,
- Dhanu Gupta,
- Duško Lainšček,
- Yonglun Luo,
- Karim Benabdellah
Affiliations
- Alessia Cavazza
- Molecular and Cellular Immunology Section, Department of Infection, Immunity & Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, 20 Guilford Street, London WC1N 1DZ, UK; Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia School of Medicine, Via del Pozzo 71, 41125 Modena, Italy; Corresponding author: Alessia Cavazza, Molecular and Cellular Immunology Section, Department of Infection, Immunity & Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, 20 Guilford Street, London WC1N 1DZ, UK.
- Francisco J. Molina-Estévez
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain; Fundación para la Investigación Biosanitaria de Andalucía Oriental, Alejandro Otero (FIBAO), Avda. de Madrid 15, 18012 Granada, Spain; Biosanitary Research Institute of Granada (ibs. GRANADA), University of Granada, Av. de Madrid, 15, Beiro, 18012 Granada, Spain
- Álvaro Plaza Reyes
- Department of Regeneration and Cell Therapy, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Avda. Americo Vespucio, 24, 41092 Seville, Spain
- Victor Ronco
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain
- Asma Naseem
- Molecular and Cellular Immunology Section, Department of Infection, Immunity & Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, 20 Guilford Street, London WC1N 1DZ, UK
- Špela Malenšek
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia; Graduate School of Biomedicine, University of Ljubljana, Kongresni trg, 1000 Ljubljana, Slovenia
- Peter Pečan
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia; Graduate School of Biomedicine, University of Ljubljana, Kongresni trg, 1000 Ljubljana, Slovenia
- Annalisa Santini
- Imagine Institute, UMR 163 INSERM, 24 Bd du Montparnasse, 75015 Paris, France; Paris City University, 45 Rue des Saints-Pères, 75006 Paris, France
- Paula Heredia
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain; Department of Anatomy and Human Embryology, Faculty of Medicine, University of Granada, Avenida de la Investigación 11, 18016 Granada, Spain
- Araceli Aguilar-González
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain; Biosanitary Research Institute of Granada (ibs. GRANADA), University of Granada, Av. de Madrid, 15, Beiro, 18012 Granada, Spain; Department of Medicinal & Organic Chemistry and Excellence Research Unit of “Chemistry applied to Bio-medicine and the Environment, ” Faculty of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Houria Boulaiz
- Biosanitary Research Institute of Granada (ibs. GRANADA), University of Granada, Av. de Madrid, 15, Beiro, 18012 Granada, Spain; Department of Anatomy and Human Embryology, Faculty of Medicine, University of Granada, Avenida de la Investigación 11, 18016 Granada, Spain
- Qianqian Ni
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
- Marina Cortijo-Gutierrez
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain
- Kristina Pavlovic
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain
- Inmaculada Herrera
- Department of Hematology, Reina Sofía University Hospital, Av. Menéndez Pidal, Poniente Sur, 14004 Córdoba, Spain; Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), Cell Therapy, Av. Menéndez Pidal, Poniente Sur, 14004 Córdoba, Spain
- Berta de la Cerda
- Department of Regeneration and Cell Therapy, Andalusian Molecular Biology and Regenerative Medicine Centre (CABIMER), Avda. Americo Vespucio, 24, 41092 Seville, Spain
- Emilio M. Garcia-Tenorio
- Centro de Biología Molecular Severo Ochoa UAM-CSIC, IUBM, CIBERER, IDIPAZ, Universidad Autónoma de Madrid, C. de Pedro Rico, 6, Fuencarral-El Pardo, 28029 Madrid, Spain
- Eva Richard
- Centro de Biología Molecular Severo Ochoa UAM-CSIC, IUBM, CIBERER, IDIPAZ, Universidad Autónoma de Madrid, C. de Pedro Rico, 6, Fuencarral-El Pardo, 28029 Madrid, Spain
- Sergio Granados-Principal
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain; Biosanitary Research Institute of Granada (ibs. GRANADA), University of Granada, Av. de Madrid, 15, Beiro, 18012 Granada, Spain; Department of Biochemistry and Molecular Biology 2, Faculty of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Arístides López-Márquez
- Neuromuscular Unit, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, C. de Sta. Rosa, 39, 08950 Barcelona, Spain; Biomedical Research Network on Rare Diseases (CIBERER), C. de Melchor Fernández Almagro, 3, Fuencarral-El Pardo, 28029 Madrid, Spain; Department of Genetics, Microbiology and Statistics, University of Barcelona, Gran Via de les Corts Catalanes, 585, L'Eixample, 08007 Barcelona, Spain
- Mariana Köber
- Biomedical Research Network on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), C/ Monforte de Lemos 3-5, Pabellón 11, Planta 0, 28029 Madrid, Spain; Institut de Ciència de Materials de Barcelona (ICMAB-CSIC), Campus UAB, Universitat Autònoma de Barcelona, 08193 Bellaterra, Barcelona, Spain
- Marijana Stojanovic
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar despota Stefana 142, 10060 Belgrade, Serbia
- Melita Vidaković
- Institute for Biological Research “Siniša Stanković”, University of Belgrade, Bulevar despota Stefana 142, 10060 Belgrade, Serbia
- Irene Santos-Garcia
- Department of Neurosciences, Biogipuzkoa Health Research Institute, Paseo Dr. Begiristain, s/n, 20014 San Sebastián, Gipuzkoa, Spain
- Lorea Blázquez
- Department of Neurosciences, Biogipuzkoa Health Research Institute, Paseo Dr. Begiristain, s/n, 20014 San Sebastián, Gipuzkoa, Spain; CIBERNED, ISCIII CIBER, Carlos III Institute, Spanish Ministry of Sciences and Innovation), Av. de Monforte de Lemos, 5, Fuencarral-El Pardo, 28029 Madrid, Spain; Ikerbasque, Basque Foundation for Science, Euskadi Pl., 5, Abando, 48009 Bilbao, Biscay, Spain
- Emily Haughton
- Institute of Developmental & Regenerative Medicine, University of Oxford, Campus, Old Rd, Roosevelt Dr, Headington, Oxford OX3 7TY, UK
- Dongnan Yan
- Institute of Developmental & Regenerative Medicine, University of Oxford, Campus, Old Rd, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Nuffield Department of Women’s and Reproductive Health, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
- Rosario María Sánchez-Martín
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain; Biosanitary Research Institute of Granada (ibs. GRANADA), University of Granada, Av. de Madrid, 15, Beiro, 18012 Granada, Spain; Department of Medicinal & Organic Chemistry and Excellence Research Unit of “Chemistry applied to Bio-medicine and the Environment, ” Faculty of Pharmacy, University of Granada, Campus de Cartuja s/n, 18071 Granada, Spain
- Loubna Mazini
- Technological, Medical and Academic Park (TMAP), N°109, Abdelkrim Elkhatabi, Bd Abdelkrim Al Khattabi, Marrakech 40000, Morocco
- Gloria Gonzalez Aseguinolaza
- DNA & RNA Medicine Division, Gene Therapy for Rare Diseases Department, Center for Applied Medical Research (CIMA), University of Navarra, IdisNA, Av. de Pío XII, 55, 31008 Pamplona, Navarra, Spain; Vivet Therapeutics, Av. de Pío XII 31, 31008 Pamplona, Navarra, Spain
- Annarita Miccio
- Imagine Institute, UMR 163 INSERM, 24 Bd du Montparnasse, 75015 Paris, France; Paris City University, 45 Rue des Saints-Pères, 75006 Paris, France
- Paula Rio
- Biomedical Research Network on Rare Diseases (CIBERER), C. de Melchor Fernández Almagro, 3, Fuencarral-El Pardo, 28029 Madrid, Spain; Division of Hematopoietic Innovative Therapies, CIEMAT, Av. Complutense, 40, Moncloa - Aravaca, 28040 Madrid, Spain; Advanced Therapies Unit, IIS-Fundación Jimenez Diaz (IIS-FJD, UAM), Av. de los Reyes Católicos, 2, Moncloa - Aravaca, 28040 Madrid, Spain
- Lourdes R. Desviat
- Centro de Biología Molecular Severo Ochoa UAM-CSIC, IUBM, CIBERER, IDIPAZ, Universidad Autónoma de Madrid, C. de Pedro Rico, 6, Fuencarral-El Pardo, 28029 Madrid, Spain
- Manuel A.F.V. Gonçalves
- Leiden University Medical Center, Department of Cell and Chemical Biology, Einthovenweg 20, 2333 ZC Leiden, the Netherlands
- Ling Peng
- Aix-Marseille Universite, CNRS, Centre Interdisciplinaire de Nanoscience de Marseille, UMR 7325, “Equipe Labellisee Ligue Ćontre le Cancer”, Campus de Luminy, case 913, 13009 Marseille, France
- Cecilia Jiménez-Mallebrera
- Neuromuscular Unit, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, C. de Sta. Rosa, 39, 08950 Barcelona, Spain; Biomedical Research Network on Rare Diseases (CIBERER), C. de Melchor Fernández Almagro, 3, Fuencarral-El Pardo, 28029 Madrid, Spain
- Francisco Martin Molina
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain; Biosanitary Research Institute of Granada (ibs. GRANADA), University of Granada, Av. de Madrid, 15, Beiro, 18012 Granada, Spain; Department of Biochemistry and Molecular Biology III and Immunology, Faculty of Medicine, University of Granada, Avenida de la Investigación 11, 18016 Granada, Spain
- Dhanu Gupta
- Institute of Developmental & Regenerative Medicine, University of Oxford, Campus, Old Rd, Roosevelt Dr, Headington, Oxford OX3 7TY, UK; Department of Laboratory Medicine, Karolinska Institutet, Alfred Nobels allé 8, 141 52 Huddinge, Sweden
- Duško Lainšček
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia; Centre for Technologies of Gene and Cell Therapy, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia; EN-FIST Centre of Excellence, Trg Osvobodilne fronte 13, 1000 Ljubljana, Slovenia
- Yonglun Luo
- Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, 8200 Aarhus N, Denmark; Corresponding author: Yonglun Luo, Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
- Karim Benabdellah
- Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain; Corresponding author: Karim Benabdellah, Department of Genomic Medicine, Pfizer-University of Granada-Andalusian Regional Government Centre for Genomics and Oncological Research (GENYO), Av. de la Ilustración, 114, 18016 Granada, Spain.
- Journal volume & issue
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Vol. 36,
no. 1
p. 102457
Abstract
In the past decade, precise targeting through genome editing has emerged as a promising alternative to traditional therapeutic approaches. Genome editing can be performed using various platforms, where programmable DNA nucleases create permanent genetic changes at specific genomic locations due to their ability to recognize precise DNA sequences. Clinical application of this technology requires the delivery of the editing reagents to transplantable cells ex vivo or to tissues and organs for in vivo approaches, often representing a barrier to achieving the desired editing efficiency and safety. In this review, authored by members of the GenE-HumDi European Cooperation in Science and Technology (COST) Action, we described the plethora of delivery systems available for genome-editing components, including viral and non-viral systems, highlighting their advantages, limitations, and potential application in a clinical setting.
