{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:51:27Z","timestamp":1787961087184,"version":"build-2784847793"},"reference-count":83,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005888","name":"Medical University of Lodz","doi-asserted-by":"crossref","award":["503\/0-166-01\/503-01-001"],"award-info":[{"award-number":["503\/0-166-01\/503-01-001"]}],"id":[{"id":"10.13039\/501100005888","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Recent years have seen rapid progress in biological treatments for genetic diseases, as well as conditions like type 1 diabetes that lack an obvious genetic component. The authors sought to explain why this progress has emerged at this particular moment. The best way to illustrate this is by showcasing a wide range of therapies targeting diverse diseases. This progress has been driven by technological advances in genetically modified CAR-T and CAR-NK cells (e.g., using CRISPR or transgenes), which have led to significant improvements in cancer therapy. A key trend now is the emergence of \u201coff-the-shelf\u201d approaches aimed at generating cellular therapies compatible with a range of recipients by mitigating alloreactivity and immune rejection. Different diseases impose distinct biological and logistical limitations; thus, treatment of each patient requires an appropriate strategy. Emerging advances include the modification of therapeutic cells, either ex vivo or in vivo. Current options for transgene delivery mainly comprise lipid nanoparticles (LNPs), adeno-associated virus (AAV) vectors, and lentiviral vectors. Researchers also focus on selecting suitable promoters for specific expression in selected cell types. Altogether, these advances have led to remarkable progress in treating various diseases in recent years. This publication discusses the development of biological therapies, with particular emphasis on cell and gene therapies, illustrated by viable examples across various disorders. It covers implemented solutions for several types of cancer, as well as selected hereditary diseases and syndromes, including Huntington\u2019s disease, carbamoyl phosphate synthetase 1 (CPS1) deficiency, hemiplegia, epidermolysis bullosa, chronic granulomatous disease, and congenital deafness. Emerging applications in heart diseases and diabetes are also summarized, along with therapeutic strategies involving tRNA gene editing. Although numerous strategies exist, only the most representative, practical, and up-to-date examples are emphasized.<\/jats:p>","DOI":"10.3390\/jcm15051799","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T10:41:02Z","timestamp":1772188862000},"page":"1799","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The New Wave of Gene and Cell Therapies Across Diseases"],"prefix":"10.3390","volume":"15","author":[{"given":"Adrianna","family":"Rieske","sequence":"first","affiliation":[{"name":"Department of Research and Development, Personather Ltd., Inwestycyjna 7 St, 95-050 Konstantynow Lodzki, Poland"},{"name":"Global Business School for Health, Faculty of Population Health Sciences, University College of London, Gower Street, London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3588-9140","authenticated-orcid":false,"given":"Dagmara","family":"Grot","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cezary","family":"Tr\u0119da","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Personather Ltd., Inwestycyjna 7 St, 95-050 Konstantynow Lodzki, Poland"},{"name":"Department of Tumor Biology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"W\u0142odarczyk","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Personather Ltd., Inwestycyjna 7 St, 95-050 Konstantynow Lodzki, Poland"},{"name":"Department of Tumor Biology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewelina","family":"Stoczy\u0144ska-Fidelus","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Jask\u00f3lska","sequence":"additional","affiliation":[{"name":"Department of Tumor Biology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2970-0970","authenticated-orcid":false,"given":"Piotr","family":"Rieske","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Personather Ltd., Inwestycyjna 7 St, 95-050 Konstantynow Lodzki, Poland"},{"name":"Department of Tumor Biology, Medical University of Lodz, Zeligowskiego 7\/9, 90-752 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"ref_1","first-page":"943","article-title":"Successes and challenges in clinical gene therapy","volume":"22","author":"Kohn","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40824-023-00381-y","article-title":"CRISPR\/Cas9 assisted stem cell therapy in Parkinson\u2019s disease","volume":"27","author":"Pinjala","year":"2023","journal-title":"Biomater. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e18359","DOI":"10.1111\/jcmm.18359","article-title":"The hope, hype and obstacles surrounding cell therapy","volume":"28","author":"Rieske","year":"2024","journal-title":"J. Cell Mol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s12967-024-06052-3","article-title":"From ex vivo to in vivo chimeric antigen T cells manufacturing","volume":"23","author":"Pinto","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ali, A., and DiPersio, J.F. (2024). ReCARving the future: Bridging CAR T-cell therapy gaps. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1432799"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105266","DOI":"10.1016\/j.ebiom.2024.105266","article-title":"Advancements and challenges in developing in vivo CAR T cell therapies for cancer treatment","volume":"106","author":"Bui","year":"2024","journal-title":"EBioMedicine"},{"key":"ref_7","unstructured":"Innovative Genomics Institute (2026, January 19). CRISPR Clinical Trials 2025. Available online: https:\/\/innovativegenomics.org\/news\/crispr-clinical-trials-2025\/."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/s41586-025-09732-2","article-title":"Prime editing-installed suppressor tRNAs for disease-agnostic genome editing","volume":"648","author":"Pierce","year":"2025","journal-title":"Nature"},{"key":"ref_9","unstructured":"Prime Medicine, Inc (2026, January 19). PM359 Clinical Data. Available online: https:\/\/investors.primemedicine.com\/news-releases\/news-release-details\/prime-medicine-announces-breakthrough-clinical-data-showing."},{"key":"ref_10","first-page":"123","article-title":"An iPSC-derived CD19\/BCMA CAR-NK therapy in a patient with systemic sclerosis","volume":"32","author":"Wang","year":"2025","journal-title":"Cell Stem Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1056\/NEJMoa2503822","article-title":"Allogeneic beta cell survival","volume":"393","author":"Carlsson","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Valayannopoulos, V., Bance, M., Carvalho, D.S., Greinwald, J.H., Harvey, S.A., Ishiyama, A., Landry, E.C., L\u00f6wenheim, H., Lustig, L.R., and Manrique, M. (2025). DB-OTO Gene Therapy for Inherited Deafness. N. Engl. J. Med.","DOI":"10.1056\/NEJMoa2400521"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s40035-025-00518-0","article-title":"Attenuating \u03b1-synuclein pathology in mice with in situ engineered astrocytes","volume":"14","author":"Du","year":"2025","journal-title":"Transl. Neurodegener."},{"key":"ref_14","unstructured":"(2026, January 19). Advances in Cell and Gene Therapy and the Evolving AAV Landscape in 2025 H1. Available online: https:\/\/www.packgene.com\/learning-center\/advances-in-cell-and-gene-therapy-and-the-evolving-aav-landscape-in-2025-h1\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1056\/NEJMoa2031054","article-title":"CRISPR\u2013Cas9 gene editing for sickle cell disease and \u03b2-thalassemia","volume":"384","author":"Frangoul","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_16","unstructured":"Beam Therapeutics (2026, January 19). Beam Therapeutics to Present Data Across Hematology Franchise. Available online: https:\/\/investors.beamtx.com\/news-releases\/news-release-details\/beam-therapeutics-present-data-across-hematology-franchise\/."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4966","DOI":"10.1097\/MS9.0000000000002409","article-title":"FDA approval of Casgevy and Lyfgenia","volume":"86","author":"Rahmat","year":"2024","journal-title":"Ann. Med. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e239","DOI":"10.1016\/S2352-3026(19)30021-3","article-title":"Lentiviral haemopoietic stem\/progenitor cell gene therapy for Wiskott\u2013Aldrich syndrome","volume":"6","author":"Ferrua","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-024-08463-0","article-title":"Engineered heart muscle allografts for heart repair in primates and humans","volume":"639","author":"Jebran","year":"2025","journal-title":"Nature"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1126\/science.adr1015","article-title":"Microglia replacement halts microgliopathy","volume":"389","author":"Wu","year":"2025","journal-title":"Science"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1016\/j.neuron.2024.05.023","article-title":"Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy","volume":"112","author":"Chadarevian","year":"2024","journal-title":"Neuron"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1038\/s41586-025-09461-6","article-title":"Therapeutic genetic restoration through allogeneic brain microglia replacement","volume":"646","author":"Mader","year":"2025","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0140-6736(00)02629-5","article-title":"Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy","volume":"356","author":"Shapiro","year":"2000","journal-title":"Lancet"},{"key":"ref_24","unstructured":"Tan, E.Y., Boelens, J.J., Jones, S.A., and Wynn, R.F. (2021). Hematopoietic Stem Cell Transplantation in Inborn Errors of Metabolism. Front. Pediatr., 9."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13036-017-0066-3","article-title":"Human pluripotent stem cell differentiation to functional pancreatic cells for diabetes therapies: Innovations, challenges and future directions","volume":"11","author":"Jacobson","year":"2017","journal-title":"J. Biol. Eng."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s11845-023-03464-w","article-title":"Donislecel-the first approved pancreatic islet cell therapy medication for type 1 diabetes: A letter to the editor","volume":"193","author":"Affan","year":"2024","journal-title":"Ir. J. Med. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41408-021-00459-7","article-title":"CAR-T cell therapy: Current limitations and potential strategies","volume":"11","author":"Sterner","year":"2021","journal-title":"Blood Cancer J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1038\/s41571-023-00754-1","article-title":"Long-term outcomes following CAR T cell therapy: What we know so far","volume":"20","author":"Cappell","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"eadg5794","DOI":"10.1126\/scitranslmed.adg5794","article-title":"Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice","volume":"15","author":"Hu","year":"2023","journal-title":"Sci. Transl. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s41587-023-01784-x","article-title":"Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques","volume":"42","author":"Hu","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1111\/dom.70330","article-title":"Safety and efficacy of the therapy with CD4\u2009+\u2009CD25highCD127-T regulatory cells: When paediatric patient becomes adult","volume":"28","author":"Bandura","year":"2026","journal-title":"Diabetes Obes. Metab."},{"key":"ref_32","unstructured":"Gori, J.L., Haddad, E., Frangoul, H., Kohn, D.B., Morris, E.C., Martin, B.N., Deary, B.A., Nickerson, M., Scholz, R.L., and Fernandez, I. (2025). Prime Editing for p47phox-Deficient Chronic Granulomatous Disease. N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s12016-020-08800-x","article-title":"Chronic Granulomatous Disease: A Comprehensive Review","volume":"61","author":"Yu","year":"2021","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_34","first-page":"225","article-title":"Prademagene zamikeracel for recessive dystrophic epidermolysis bullosa wounds (VIITAL): A two-centre, randomised, open-label, intrapatient-controlled phase 3 trial","volume":"401","author":"Tang","year":"2023","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/s41573-025-01291-5","article-title":"In vivo chimeric antigen receptor (CAR)-T cell therapy","volume":"25","author":"Bot","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/s11940-017-0444-7","article-title":"Diagnosis and treatment of alternating hemiplegia of childhood","volume":"19","author":"Masoud","year":"2017","journal-title":"Curr. Treat. Options Neurol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4275","DOI":"10.1016\/j.cell.2025.06.038","article-title":"In vivo prime editing rescues alternating hemiplegia of childhood in mice","volume":"188","author":"Sousa","year":"2025","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Rissardo, J.P., Vora, N.M., Singh, Y., Kishore, S., and Caprara, A.L.F. (2024). Navigating the complexity of alternating hemiplegia in childhood: A comprehensive review. Front. Neurol., 15.","DOI":"10.5041\/RMMJ.10529"},{"key":"ref_39","unstructured":"Children\u2019s Hospital of Philadelphia (2026, January 18). World\u2019s First Patient Treated with Personalized CRISPR Gene Editing Therapy. Available online: https:\/\/www.chop.edu\/news\/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Vega, M.G., Andrade, J.D., Morais, A., Frauca, E., Bartolo, G.M., Lled\u00edn, M.D., Bergua, A., and Hierro, L. (2023). Urea cycle disorders and indications for liver transplantation. Front. Pediatr., 11.","DOI":"10.3389\/fped.2023.1103757"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1002\/lt.26186","article-title":"Liver transplantation in children with urea cycle disorders: The importance of minimizing waiting time","volume":"27","author":"Ziogas","year":"2021","journal-title":"Liver Transplant."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Ledford, H. (2025). World\u2019s First Personalized CRISPR Therapy Given to Baby with Genetic Disease. Nature, Available online: https:\/\/www.nature.com\/articles\/d41586-025-01496-z.","DOI":"10.1038\/d41586-025-01496-z"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Whittaker, M.N., Testa, L.C., Quigley, A., Brooks, D.L., Grandinette, S.A., Said, H., Dwivedi, G., Jindal, I., Volpp, D., and Hacker, J.L. (2025). Improved specificity and efficiency of in vivo adenine base editing therapies with hybrid guide RNAs. Nat. Biomed. Eng., 1\u201313.","DOI":"10.1038\/s41551-025-01545-y"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1089\/hum.2024.106","article-title":"Lipid nanoparticles for nucleic acid delivery beyond the liver","volume":"35","author":"Saber","year":"2024","journal-title":"Hum. Gene Ther."},{"key":"ref_45","unstructured":"Oligonucleotide Therapeutics Society (2026, January 19). Behind the Rapid Development of an Individualized CRISPR Therapy for a Deadly Rare Disease. Available online: https:\/\/oligotherapeutics.org\/behind-the-rapid-development-of-an-individualized-crispr-therapy-for-a-deadly-rare-disease\/."},{"key":"ref_46","unstructured":"OC Academy (2025, November 09). Game Changer: FDA Fast-Tracks Personalized Gene Editing Therapies. Available online: https:\/\/www.ocacademy.in\/blogs\/fda-fast-tracks-personalised-gene-editing-therapy\/."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1056\/NEJMoa2511778","article-title":"Phase 1 trial of CRISPR\u2013Cas9 gene editing targeting ANGPTL3","volume":"393","author":"Laffin","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4394","DOI":"10.1016\/j.ymthe.2025.06.017","article-title":"Precise progerin targeting using RfxCas13d: A therapeutic avenue for Hutchinson\u2013Gilford progeria syndrome","volume":"33","author":"Chae","year":"2025","journal-title":"Mol. Ther."},{"key":"ref_49","unstructured":"Gordon, L.B., Brown, W.T., and Collins, F.S. (2023). Hutchinson\u2013Gilford progeria syndrome. GeneReviews\u00ae, University of Washington."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"R652","DOI":"10.1016\/j.cub.2006.07.029","article-title":"Aging: Progeria and the lamin connection","volume":"16","author":"Kudlow","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_51","unstructured":"uniQure (2026, January 19). Phase I\/II Clinical Trial of AMT-130. Available online: https:\/\/www.uniqure.com\/programs-pipeline\/phase-1-2-clinical-trial-of-amt-130."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e210268","DOI":"10.1212\/WNL.0000000000210268","article-title":"Safety and efficacy of IV onasemnogene abeparvovec for pediatric patients with spinal muscular atrophy: The phase 3b SMART study","volume":"104","author":"McMillan","year":"2025","journal-title":"Neurology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1089\/hum.2004.15.896","article-title":"Trans-splicing adeno-associated viral vector-mediated gene therapy is limited by the accumulation of spliced mRNA but not by dual vector coinfection efficiency","volume":"15","author":"Xu","year":"2004","journal-title":"Hum. Gene Ther."},{"key":"ref_54","unstructured":"Sarepta Therapeutics (2026, January 19). Sarepta Announces Positive Topline Three-Year EMBARK Results. Available online: https:\/\/investorrelations.sarepta.com\/news-releases\/news-release-details\/sarepta-announces-positive-topline-three-year-embark-results."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/s41586-023-06133-1","article-title":"Engineered tRNAs suppress nonsense mutations in cells and in vivo","volume":"618","author":"Albers","year":"2023","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/s41573-023-00829-9","article-title":"tRNA therapeutics for genetic diseases","volume":"23","author":"Coller","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s40164-023-00435-w","article-title":"Current approaches to develop off-the-shelf chimeric antigen receptor (CAR)-T cells for cancer treatment: A systematic review","volume":"12","author":"Aparicio","year":"2023","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.stem.2025.07.009","article-title":"Hypoimmune CD19 CAR T cells evade allorejection in patients with cancer and autoimmune disease","volume":"32","author":"Hu","year":"2025","journal-title":"Cell Stem Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"15002","DOI":"10.1038\/nrdp.2015.2","article-title":"Systemic sclerosis","volume":"1","author":"Allanore","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.medj.2025.100804","article-title":"Overcoming ovarian cancer resistance and evasion to CAR-T cell therapy by harnessing allogeneic CAR-NKT cells","volume":"6","author":"Li","year":"2025","journal-title":"Med"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1056\/NEJMoa2300709","article-title":"Base-Edited CAR7 T Cells for Relapsed T-Cell Acute Lymphoblastic Leukemia","volume":"389","author":"Chiesa","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_62","unstructured":"(2026, January 19). ClinicalTrials.gov. Study NCT03294954, Available online: https:\/\/clinicaltrials.gov\/study\/NCT03294954."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101612","DOI":"10.1016\/j.gendis.2025.101612","article-title":"In vivo production of CAR T cells: Opportunities and challenges","volume":"12","author":"Song","year":"2025","journal-title":"Genes Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1056\/NEJMra1706169","article-title":"Chimeric Antigen Receptor Therapy","volume":"379","author":"June","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1126\/science.abm0594","article-title":"CAR T cells produced in vivo to treat cardiac injury","volume":"375","author":"Rurik","year":"2022","journal-title":"Science"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Shah, M., Krull, A., Odonnell, L., de Lima, M.J., and Bezerra, E. (2023). Promises and challenges of a decentralized CAR T-cell manufacturing model. Front. Transplant., 2.","DOI":"10.3389\/frtra.2023.1238535"},{"key":"ref_67","first-page":"1","article-title":"High Cost of Chimeric Antigen Receptor T-Cells: Challenges and Solutions","volume":"43","author":"Cliff","year":"2023","journal-title":"ASCO Educ. Book"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.tips.2024.03.004","article-title":"Direct in vivo CAR T cell engineering","volume":"45","author":"Short","year":"2024","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40364-026-00899-y","article-title":"In vivo engineering of CAR-T cells: Delivery strategies and clinical translation","volume":"14","author":"Gao","year":"2026","journal-title":"Biomark. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1126\/science.ads8473","article-title":"In vivo CAR T cell generation to treat cancer and autoimmune disease","volume":"388","author":"Hunter","year":"2025","journal-title":"Science"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"100040","DOI":"10.1016\/j.nbe.2025.100040","article-title":"Antibody-conjugated lipid nanoparticles for in vivo CAR-T cell engineering: From concept to clinical translation","volume":"18","author":"Guo","year":"2026","journal-title":"Nano Biomed. Eng."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1186\/s12943-022-01559-z","article-title":"Engineering the next-generation of CAR T-cells with CRISPR\u2013Cas9 gene editing","volume":"21","author":"Dimitri","year":"2022","journal-title":"Mol. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1186\/s40164-025-00725-5","article-title":"In vivo CAR-T cell engineering: Concept, research progress, potential challenges and enhancement strategies","volume":"14","author":"Chen","year":"2025","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"eadj6251","DOI":"10.1126\/sciadv.adj6251","article-title":"Enhancing the safety of CAR-T cell therapy: Synthetic genetic switch for spatiotemporal control","volume":"10","author":"Lu","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Liu, J., Zhou, G., Zhang, L., and Zhao, Q. (2019). Building potent chimeric antigen receptor T cells with CRISPR genome editing. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00456"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Fang, M., Allen, A., Luo, C., and Finn, J.D. (2024). Unlocking the potential of iPSC-derived immune cells. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1457629"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8350","DOI":"10.1038\/s41467-024-52599-6","article-title":"Massively parallel characterization of insulator activity across the genome","volume":"15","author":"Hong","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.omtm.2023.08.015","article-title":"Modifying immune responses to adeno-associated virus vectors by capsid engineering","volume":"30","author":"Bentler","year":"2023","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1002\/stem.2725","article-title":"A Novel Construction of Lentiviral Vectors for Eliminating Tumorigenic Cells from Pluripotent Stem Cells","volume":"36","author":"Ide","year":"2018","journal-title":"Stem Cells"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1056\/NEJMe2507578","article-title":"Replacement of Beta Cells for Type 1 Diabetes","volume":"393","author":"Herold","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1056\/NEJMoa2506549","article-title":"Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes","volume":"393","author":"Reichman","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2235","DOI":"10.1056\/NEJMoa2504747","article-title":"Patient-specific in vivo gene editing to treat a rare genetic disease","volume":"392","author":"Musunuru","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Artemyev, V., Paremskaia, A.I., Dzhioeva, A.A., Mishina, D., Bogdanov, V., Krupinova, J., Mazloum, A., Feoktistova, S.G., Mityaeva, O.N., and Volchkov, P.Y. (2025). Engineering Liver-Specific Promoters: A Comprehensive Review of Design, Mechanisms, and Clinical Applications in Gene Therapy. Cells, 15.","DOI":"10.3390\/cells15010014"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/5\/1799\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T05:24:56Z","timestamp":1772342696000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/5\/1799"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,27]]},"references-count":83,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["jcm15051799"],"URL":"https:\/\/doi.org\/10.3390\/jcm15051799","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,27]]}}}