{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T02:13:42Z","timestamp":1781662422270,"version":"3.54.5"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T00:00:00Z","timestamp":1641340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011852","name":"Paracelsus Medical University","doi-asserted-by":"publisher","award":["E-14\/19\/098GRU"],"award-info":[{"award-number":["E-14\/19\/098GRU"]}],"id":[{"id":"10.13039\/501100011852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Conventional anti-cancer therapies based on chemo- and\/or radiotherapy represent highly effective means to kill cancer cells but lack tumor specificity and, therefore, result in a wide range of iatrogenic effects. A promising approach to overcome this obstacle is spliceosome-mediated RNA trans-splicing (SMaRT), which can be leveraged to target tumor cells while leaving normal cells unharmed. Notably, a previously established RNA trans-splicing molecule (RTM44) showed efficacy and specificity in exchanging the coding sequence of a cancer target gene (Ct-SLCO1B3) with the suicide gene HSV1-thymidine kinase in a colorectal cancer model, thereby rendering tumor cells sensitive to the prodrug ganciclovir (GCV). In the present work, we expand the application of this approach, using the same RTM44 in aggressive skin cancer arising in the rare genetic skin disease recessive dystrophic epidermolysis bullosa (RDEB). Stable expression of RTM44, but not a splicing-deficient control (NC), in RDEB-SCC cells resulted in expression of the expected fusion product at the mRNA and protein level. Importantly, systemic GCV treatment of mice bearing RTM44-expressing cancer cells resulted in a significant reduction in tumor volume and weight compared with controls. Thus, our results demonstrate the applicability of RTM44-mediated targeting of the cancer gene Ct-SLCO1B3 in a different malignancy.<\/jats:p>","DOI":"10.3390\/ijms23010575","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T01:15:26Z","timestamp":1641518126000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Evaluating a Targeted Cancer Therapy Approach Mediated by RNA trans-Splicing In Vitro and in a Xenograft Model for Epidermolysis Bullosa-Associated Skin Cancer"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6189-2733","authenticated-orcid":false,"given":"Katharina","family":"Woess","sequence":"first","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5452-8829","authenticated-orcid":false,"given":"Yuchen","family":"Sun","sequence":"additional","affiliation":[{"name":"Division of Medicinal Safety Science, National Institute of Health Sciences, Kanagawa 210-9501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanae","family":"Morio","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacy and Experimental Therapeutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0355, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Stierschneider","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Hainzl","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Trattner","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3424-3049","authenticated-orcid":false,"given":"Thomas","family":"Kocher","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit","family":"Tockner","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Leb-Reichl","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III with Haematology, Medical Oncology, Haemostaseology Infectiology and Rheumatology, Oncologic Center, Salzburg Cancer Research Institute-Laboratory for Immunological and Molecular Cancer Research (LIMCR), Cancer Cluster Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Brachtl","sequence":"additional","affiliation":[{"name":"Cell Therapy Institute, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"South","sequence":"additional","affiliation":[{"name":"Dermatology and Cutaneous Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann W.","family":"Bauer","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4358-7011","authenticated-orcid":false,"given":"Julia","family":"Reichelt","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Furihata","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacy and Experimental Therapeutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0355, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8705-3890","authenticated-orcid":false,"given":"Verena","family":"Wally","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6285-1789","authenticated-orcid":false,"given":"Ulrich","family":"Koller","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8558-9031","authenticated-orcid":false,"given":"Josefina","family":"Pi\u00f1\u00f3n Hofbauer","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8232-5068","authenticated-orcid":false,"given":"Christina","family":"Guttmann-Gruber","sequence":"additional","affiliation":[{"name":"EB House Austria, Research Program for Molecular Therapy of Genodermatoses, Department of Dermatology and Allergology, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1093\/gbe\/evw025","article-title":"Evolutionary Insights into RNA trans-Splicing in Vertebrates","volume":"8","author":"Lei","year":"2016","journal-title":"Genome. Biol. Evol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.trecan.2016.07.006","article-title":"Intergenically Spliced Chimeric RNAs in Cancer","volume":"2","author":"Jia","year":"2016","journal-title":"Trends Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9172","DOI":"10.1073\/pnas.1100489108","article-title":"Recurrent chimeric RNAs enriched in human prostate cancer identified by deep sequencing","volume":"108","author":"Kannan","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.gde.2017.10.002","article-title":"Chimeric RNAs and their implications in cancer","volume":"48","author":"Li","year":"2018","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/6986","article-title":"Spliceosome-mediated RNA trans-splicing as a tool for gene therapy","volume":"17","author":"Puttaraju","year":"1999","journal-title":"Nat. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/bjd.17075","article-title":"An ex vivo RNA trans-splicing strategy to correct human generalized severe epidermolysis bullosa simplex","volume":"180","author":"Peking","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1038\/sj.jid.5701152","article-title":"5\u2032 trans-splicing repair of the PLEC1 gene","volume":"128","author":"Wally","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/jid.2010.249","article-title":"Functional correction of type VII collagen expression in dystrophic epidermolysis bullosa","volume":"131","author":"Murauer","year":"2011","journal-title":"J. Investig. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10259","DOI":"10.1093\/nar\/gkx669","article-title":"An RNA-targeted therapy for dystrophic epidermolysis bullosa","volume":"45","author":"Peking","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/gt.2016.57","article-title":"Construction and validation of an RNA trans-splicing molecule suitable to repair a large number of COL7A1 mutations","volume":"23","author":"Tockner","year":"2016","journal-title":"Gene Ther."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Huttner, C., Murauer, E.M., Hainzl, S., Kocher, T., Neumayer, A., Reichelt, J., Bauer, J.W., and Koller, U. (2016). Designing Efficient Double RNA trans-Splicing Molecules for Targeted RNA Repair. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17101609"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1093\/nar\/gkr465","article-title":"A novel screening system improves genetic correction by internal exon replacement","volume":"39","author":"Koller","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1093\/bmb\/ldaa028","article-title":"Therapeutic applications of trans-splicing","volume":"136","author":"Hong","year":"2020","journal-title":"Br. Med. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.molonc.2013.08.005","article-title":"The design and optimization of RNA trans-splicing molecules for skin cancer therapy","volume":"7","author":"Gruber","year":"2013","journal-title":"Mol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.omtn.2017.03.004","article-title":"Expression of Herpes Simplex Virus Thymidine Kinase\/Ganciclovir by RNA Trans-Splicing Induces Selective Killing of HIV-Producing Cells","volume":"7","author":"Ingemarsdotter","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.omtn.2018.01.006","article-title":"RNA Structure Design Improves Activity and Specificity of trans-Splicing-Triggered Cell Death in a Suicide Gene Therapy Approach","volume":"11","author":"Poddar","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.canlet.2018.06.032","article-title":"Cancer-type organic anion transporting polypeptide 1B3 is a target for cancer suicide gene therapy using RNA trans-splicing technology","volume":"433","author":"Sun","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2174\/1566523033347426","article-title":"Suicide gene therapy mediated by the Herpes Simplex virus thymidine kinase gene\/Ganciclovir system: Fifteen years of application","volume":"3","author":"Fillat","year":"2003","journal-title":"Curr. Gene Ther."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1158\/1535-7163.MCT-10-0669","article-title":"Spliceosome-mediated RNA trans-splicing facilitates targeted delivery of suicide genes to cancer cells","volume":"10","author":"Gruber","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/1872312812666180326110146","article-title":"Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues","volume":"12","author":"Alam","year":"2018","journal-title":"Drug Metab. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.bbrc.2012.01.115","article-title":"Identification of a new organic anion transporting polypeptide 1B3 mRNA isoform primarily expressed in human cancerous tissues and cells","volume":"418","author":"Nagai","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1021\/mp3005353","article-title":"A cancer-specific variant of the SLCO1B3 gene encodes a novel human organic anion transporting polypeptide 1B3 (OATP1B3) localized mainly in the cytoplasm of colon and pancreatic cancer cells","volume":"10","author":"Thakkar","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/j.jid.2017.11.022","article-title":"Extracellular Vesicles as Biomarkers for the Detection of a Tumor Marker Gene in Epidermolysis Bullosa-Associated Squamous Cell Carcinoma","volume":"138","author":"Sun","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41572-020-0210-0","article-title":"Epidermolysis bullosa","volume":"6","author":"Bardhan","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jaad.2008.09.035","article-title":"Epidermolysis bullosa and the risk of life-threatening cancers: The National EB Registry experience, 1986\u20132006","volume":"60","author":"Fine","year":"2009","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1001\/jamadermatol.2016.2473","article-title":"Epidemiology of Inherited Epidermolysis Bullosa Based on Incidence and Prevalence Estimates From the National Epidermolysis Bullosa Registry","volume":"152","author":"Fine","year":"2016","journal-title":"JAMA Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2340\/00015555-2781","article-title":"Epidemiology and Outcome of Squamous Cell Carcinoma in Epidermolysis Bullosa in Australia and New Zealand","volume":"98","author":"Kim","year":"2018","journal-title":"Acta Derm. Venereol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cho, R.J., Alexandrov, L.B., den Breems, N.Y., Atanasova, V.S., Farshchian, M., Purdom, E., Nguyen, T.N., Coarfa, C., Rajapakshe, K., and Prisco, M. (2018). APOBEC mutation drives early-onset squamous cell carcinomas in recessive dystrophic epidermolysis bullosa. Sci. Transl. Med., 10.","DOI":"10.1016\/j.jid.2017.07.734"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/0042-6822(88)90308-X","article-title":"Site-directed mutagenesis of a nucleotide-binding domain in HSV-1 thymidine kinase: Effects on catalytic activity","volume":"163","author":"Liu","year":"1988","journal-title":"Virology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1684\/ejd.2015.2552","article-title":"Update on the pathogenesis of squamous cell carcinoma development in recessive dystrophic epidermolysis bullosa","volume":"25","author":"Kim","year":"2015","journal-title":"Eur. J. Dermatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1038\/nm900","article-title":"Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing","volume":"9","author":"Chao","year":"2003","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.omtn.2018.05.014","article-title":"Spliceosome-Mediated Pre-mRNA trans-Splicing Can Repair CEP290 mRNA","volume":"12","author":"Dooley","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nbt0102-47","article-title":"Partial correction of endogenous DeltaF508 CFTR in human cystic fibrosis airway epithelia by spliceosome-mediated RNA trans-splicing","volume":"20","author":"Liu","year":"2002","journal-title":"Nat. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3389\/fnins.2017.00544","article-title":"Optimization of trans-Splicing for Huntington\u2019s Disease RNA Therapy","volume":"11","author":"Rindt","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nm1086","article-title":"Trans-splicing repair of CD40 ligand deficiency results in naturally regulated correction of a mouse model of hyper-IgM X-linked immunodeficiency","volume":"10","author":"Tahara","year":"2004","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e362","DOI":"10.1038\/mtna.2016.67","article-title":"Reprogramming the Dynamin 2 mRNA by Spliceosome-mediated RNA Trans-splicing","volume":"5","author":"Trochet","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0092-8674(78)90099-5","article-title":"One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell","volume":"15","author":"Yamaizumi","year":"1978","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.canlet.2008.04.023","article-title":"Prodrug cancer gene therapy","volume":"270","author":"Altaner","year":"2008","journal-title":"Cancer Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/38410","article-title":"Gene therapy\u2014Promises, problems and prospects","volume":"389","author":"Verma","year":"1997","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ymgme.2003.08.016","article-title":"Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer","volume":"80","author":"Raper","year":"2003","journal-title":"Mol. Genet. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/S1525-0016(03)00168-0","article-title":"Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo","volume":"8","author":"Chen","year":"2003","journal-title":"Mol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113842","DOI":"10.1016\/j.addr.2021.113842","article-title":"Highly branched poly(beta-amino ester)s for gene delivery in hereditary skin diseases","volume":"176","author":"Zeng","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1146\/annurev.bioeng.2.1.289","article-title":"Microfabricated microneedles for gene and drug delivery","volume":"2","author":"McAllister","year":"2000","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e287","DOI":"10.1038\/mtna.2016.3","article-title":"A Gene Gun-mediated Nonviral RNA trans-splicing Strategy for Col7a1 Repair","volume":"5","author":"Peking","year":"2016","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"32182","DOI":"10.18632\/oncotarget.25875","article-title":"Sonoporation by microbubbles as gene therapy approach against liver cancer","volume":"9","author":"Rinaldi","year":"2018","journal-title":"Oncotarget"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/575\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:26:48Z","timestamp":1760362008000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/575"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,5]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010575"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010575","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,5]]}}}