{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:24Z","timestamp":1792789104077,"version":"4.5.0"},"reference-count":98,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T00:00:00Z","timestamp":1734307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Russian Federation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Adenoviral vectors (AdVs) are effective vectors for gene therapy due to their broad tropism, high capacity, and high transduction efficiency, which makes them actively used as oncolytic vectors and for creating vector vaccines. However, despite their numerous advantages, AdVs have not yet found their place in gene therapy for hereditary diseases. This review provides an overview of AdVs, their features, and clinical trials using them for gene replacement therapy in monogenic diseases and analyzes the reasons for the failures of these studies. Additionally, current research on the modification of AdVs to reduce immune responses and target delivery is discussed.<\/jats:p>","DOI":"10.3390\/biology13121052","type":"journal-article","created":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T04:14:52Z","timestamp":1734322492000},"page":"1052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Adenoviral Vectors for Gene Therapy of Hereditary Diseases"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6520-3917","authenticated-orcid":false,"given":"Anna","family":"Muravyeva","sequence":"first","affiliation":[{"name":"Laboratory of Genome Editing, Research Centre for Medical Genetics, Moskvorechye, 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Smirnikhina","sequence":"additional","affiliation":[{"name":"Laboratory of Genome Editing, Research Centre for Medical Genetics, Moskvorechye, 1, 115522 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0065-230X(08)60995-1","article-title":"Transcriptional and Transforming Activities of the Adenovirus E1A Proteins","volume":"57","author":"Shenk","year":"1991","journal-title":"Adv. Cancer Res."},{"key":"ref_2","first-page":"177","article-title":"Regulation of Adenovirus E2 Transcription Unit","volume":"199","author":"Swaminathan","year":"1995","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S172","DOI":"10.1002\/jgm.495","article-title":"Function of Adenovirus E3 Proteins and Their Interactions with Immunoregulatory Cell Proteins","volume":"6","author":"Horwitz","year":"2004","journal-title":"J. Gene Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.2741\/1604","article-title":"Functions of the Adenovirus E4 Proteins and Their Impact on Viral Vectors","volume":"10","author":"Weitzman","year":"2005","journal-title":"Front. Biosci."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ison, M.G., and Hayden, R.T. (2016). Adenovirus. Diagnostic Microbiology of the Immunocompromised Host, Wiley Online Library.","DOI":"10.1128\/9781555819040.ch10"},{"key":"ref_6","unstructured":"HAdV Working Group (2024, November 21). Available online: http:\/\/hadvwg.gmu.edu\/."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1099\/vir.0.19497-0","article-title":"Genetic Content and Evolution of Adenoviruses","volume":"84","author":"Davison","year":"2003","journal-title":"J. Gen. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1016\/S0140-6736(20)32270-4","article-title":"ChAdOx1 NCoV-19 Vaccine for SARS-CoV-2","volume":"396","author":"Lodge","year":"2020","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7909","DOI":"10.1128\/JVI.72.10.7909-7915.1998","article-title":"The Coxsackievirus-Adenovirus Receptor Protein Can Function as a Cellular Attachment Protein for Adenovirus Serotypes from Subgroups A, C, D, E, and F","volume":"72","author":"Roelvink","year":"1998","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-3527(08)60556-4","article-title":"Adenoviruses: The Nature of the Virion and of Controlling Factors in Productive or Abortive Infection and Tumorigenesis","volume":"14","author":"Schlesinger","year":"1969","journal-title":"Adv. Virus Res."},{"key":"ref_11","first-page":"59","article-title":"Adenoviruses","volume":"2","author":"Hidalgo","year":"2022","journal-title":"Encycl. Infect. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sayedahmed, E.E., Kumari, R., and Mittal, S.K. (2019). Current Use of Adenovirus Vectors and Their Production Methods. Methods Mol. Biol., 1937.","DOI":"10.1007\/978-1-4939-9065-8_9"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1080\/22221751.2019.1690953","article-title":"Are Adenoviruses Zoonotic? A Systematic Review of the Evidence","volume":"8","author":"Borkenhagen","year":"2019","journal-title":"Emerg. Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0378-1119(02)00410-9","article-title":"Adenovirus Vectors Containing Chimeric Type 5 and Type 35 Fiber Proteins Exhibit Altered and Expanded Tropism and Increase the Size Limit of Foreign Genes","volume":"285","author":"Mizuguchi","year":"2002","journal-title":"Gene"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4612","DOI":"10.1128\/JVI.76.9.4612-4620.2002","article-title":"Exploiting the Natural Diversity in Adenovirus Tropism for Therapy and Prevention of Disease","volume":"76","author":"Havenga","year":"2002","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e3015","DOI":"10.1002\/jgm.3015","article-title":"Gene Therapy Clinical Trials Worldwide to 2017: An Update","volume":"20","author":"Ginn","year":"2018","journal-title":"J. Gene Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1126\/science.275.5304.1320","article-title":"Isolation of a Common Receptor for Coxsackie B Viruses and Adenoviruses 2 and 5","volume":"275","author":"Bergelson","year":"1997","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6141","DOI":"10.1128\/JVI.73.7.6141-6146.1999","article-title":"Frequency and Stability of Chromosomal Integration of Adenovirus Vectors","volume":"73","author":"Harui","year":"1999","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.2174\/1566523013348689","article-title":"Adenoviral Vector-Mediated Gene Transfer for Human Gene Therapy","volume":"1","author":"Breyer","year":"2001","journal-title":"Curr. Gene Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.virol.2016.12.021","article-title":"Adenovirus-Vectored Foot-and-Mouth Disease Vaccine Confers Early and Full Protection against FMDV O1 Manisa in Swine","volume":"502","author":"Medina","year":"2017","journal-title":"Virology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1172\/JCI116614","article-title":"Adenoviral-Mediated Gene Transfer to Rabbit Synovium in Vivo","volume":"92","author":"Roessler","year":"1993","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0304-3940(96)12499-X","article-title":"Adenoviral-Mediated Gene Transfer into Guinea Pig Cochlear Cells in Vivo","volume":"207","author":"Raphael","year":"1996","journal-title":"Neurosci. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1089\/hum.1998.9.5-629","article-title":"High-Level Dystrophin Expression after Adenovirus-Mediated Dystrophin Minigene Transfer to Skeletal Muscle of Dystrophic Dogs: Prolongation of Expression with Immunosuppression","volume":"9","author":"Howell","year":"1998","journal-title":"Hum. Gene Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S1072-7515(98)00163-X","article-title":"Efficient Inhibition of Intimal Hyperplasia by Adenovirus-Mediated Inducible Nitric Oxide Synthase Gene Transfer to Rats and Pigs in Vivo","volume":"187","author":"Shears","year":"1998","journal-title":"J. Am. Coll. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/s41541-021-00356-x","article-title":"Adenoviral Vector Vaccine Platforms in the SARS-CoV-2 Pandemic","volume":"6","author":"Lorincz","year":"2021","journal-title":"npj Vaccines"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1128\/JVI.78.6.2666-2673.2004","article-title":"Neutralizing Antibodies and CD8 + T Lymphocytes Both Contribute to Immunity to Adenovirus Serotype 5 Vaccine Vectors","volume":"78","author":"Sumida","year":"2004","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/rr6","article-title":"Size Does Matter: Overcoming the Adeno-Associated Virus Packaging Limit","volume":"1","author":"Flotte","year":"2000","journal-title":"Respir. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jayandharan, G.R. (2018). Adeno-Associated Virus Vectors in Gene Therapy. Gene and Cell Therapy: Biology and Applications, Springer.","DOI":"10.1007\/978-981-13-0481-1"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1007\/s00109-021-02086-y","article-title":"Tissue and Cell-Type-Specific Transduction Using RAAV Vectors in Lung Diseases","volume":"99","author":"Belova","year":"2021","journal-title":"J. Mol. Med."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Li, L., Vasan, L., Kartono, B., Clifford, K., Attarpour, A., Sharma, R., Mandrozos, M., Kim, A., Zhao, W., and Belotserkovsky, A. (2023). Advances in Recombinant Adeno-Associated Virus Vectors for Neurodegenerative Diseases. Biomedicines, 11.","DOI":"10.3390\/biomedicines11102725"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8802","DOI":"10.1073\/pnas.91.19.8802","article-title":"An Efficient and Flexible System for Construction of Adenovirus Vectors with Insertions or Deletions in Early Regions 1 and 3","volume":"91","author":"Bett","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1006\/viro.1997.8597","article-title":"Cloning and Sequencing of the Cellular-Viral Junctions from the Human Adenovirus Type 5 Transformed 293 Cell Line","volume":"233","author":"Louis","year":"1997","journal-title":"Virology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5437","DOI":"10.1128\/JVI.79.9.5437-5444.2005","article-title":"Replication-Competent Adenovirus Formation in 293 Cells: The Recombination-Based Rate Is Influenced by Structure and Location of the Transgene Cassette and Not Increased by Overproduction of HsRad51, Rad51-Interacting, or E2F Family Proteins","volume":"79","author":"Duigou","year":"2005","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1128\/JVI.72.2.926-933.1998","article-title":"Production and Characterization of Improved Adenovirus Vectors with the E1, E2b, and E3 Genes Deleted","volume":"72","author":"Amalfitano","year":"1998","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2174\/156652307780859062","article-title":"Current Advances and Future Challenges in Adenoviral Vector Biology and Targeting","volume":"7","author":"Campos","year":"2007","journal-title":"Curr. Gene Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1073\/pnas.95.5.2509","article-title":"A Simplified System for Generating Recombinant Adenoviruses","volume":"95","author":"He","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","first-page":"454","article-title":"High-Capacity \u201cgutless\u201d Adenoviral Vectors","volume":"3","author":"Kochanek","year":"2001","journal-title":"Curr. Opin. Mol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1089\/hum.2007.124","article-title":"Replication-Competent Ad11p Vector (RCAd11p) Efficiently Transduces and Replicates in Hormone-Refractory Metastatic Prostate Cancer Cells","volume":"20","author":"Mei","year":"2009","journal-title":"Hum. Gene Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.gendis.2017.04.001","article-title":"Adenovirus-Mediated Gene Delivery: Potential Applications for Gene and Cell-Based Therapies in the New Era of Personalized Medicine","volume":"4","author":"Lee","year":"2017","journal-title":"Genes Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41576-019-0205-4","article-title":"Engineering Adeno-Associated Virus Vectors for Gene Therapy","volume":"21","author":"Li","year":"2020","journal-title":"Nat. Rev. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1016\/S1525-0016(16)33110-0","article-title":"301. AAV Capsid Engineering to Improve Transduction in Retina and Brain","volume":"24","author":"Sullivan","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1099\/vir.0.83057-0","article-title":"Evidence of Frequent Recombination among Human Adenoviruses","volume":"89","author":"Lukashev","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.omtm.2019.11.001","article-title":"Immunology of Adenoviral Vectors in Cancer Therapy","volume":"15","author":"Shaw","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4297","DOI":"10.1158\/0008-5472.CAN-09-3567","article-title":"Oncolytic Adenovirus Coding for Granulocyte Macrophage Colony-Stimulating Factor Induces Antitumoral Immunity in Cancer Patients","volume":"70","author":"Cerullo","year":"2010","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"100432","DOI":"10.1016\/j.dmpk.2021.100432","article-title":"Adenovirus Vector-Based Vaccine for Infectious Diseases","volume":"42","author":"Sakurai","year":"2022","journal-title":"Drug Metab. Pharmacokinet."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Chavda, V.P., Bezbaruah, R., Valu, D., Patel, B., Kumar, A., Prasad, S., Kakoti, B.B., Kaushik, A., and Jesawadawala, M. (2023). Adenoviral Vector-Based Vaccine Platform for COVID-19: Current Status. Vaccines, 11.","DOI":"10.3390\/vaccines11020432"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Zhao, Z., Anselmo, A.C., and Mitragotri, S. (2021). Viral Vector-Based Gene Therapies in the Clinic. Bioeng. Transl. Med., 7.","DOI":"10.1002\/btm2.10258"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1126\/science.2475911","article-title":"Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNA","volume":"245","author":"Riordan","year":"1989","journal-title":"Science"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1016\/0092-8674(93)90353-R","article-title":"Molecular Mechanisms of CFTR Chloride Channel Dysfunction in Cystic Fibrosis","volume":"73","author":"Welsh","year":"1993","journal-title":"Cell"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.1089\/10430349950016384","article-title":"A Phase I Study of Adenovirus-Mediated Transfer of the Human Cystic Fibrosis Transmembrane Conductance Regulator Gene to a Lung Segment of Individuals with Cystic Fibrosis","volume":"10","author":"Zuckerman","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1056\/NEJM199509283331302","article-title":"A Controlled Study of Adenoviral-Vector-Mediated Gene Transfer in the Nasal Epithelium of Patients with Cystic Fibrosis","volume":"333","author":"Knowles","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1172\/JCI117789","article-title":"Normalization of Raised Sodium Absorption and Raised Calcium-Mediated Chloride Secretion by Adenovirus-Mediated Expression of Cystic Fibrosis Transmembrane Conductance Regulator in Primary Human Cystic Fibrosis Airway Epithelial Cells","volume":"95","author":"Johnson","year":"1995","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1089\/hum.1994.5.7-821","article-title":"Acute Responses of Non-Human Primates to Airway Delivery of an Adenovirus Vector Containing the Human Cystic Fibrosis Transmembrane Conductance Regulator CDNA","volume":"5","author":"Brody","year":"1994","journal-title":"Hum. Gene Ther."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1172\/JCI7935","article-title":"Airway Epithelial CFTR MRNA Expression in Cystic Fibrosis Patients after Repetitive Administration of a Recombinant Adenovirus","volume":"104","author":"Harvey","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.addr.2008.09.008","article-title":"Barrier Properties of Mucus","volume":"61","author":"Cone","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.addr.2008.11.002","article-title":"Mucus-Penetrating Nanoparticles for Drug and Gene Delivery to Mucosal Tissues","volume":"61","author":"Lai","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/mt.2012.32","article-title":"Advances in Cell and Gene-Based Therapies for Cystic Fibrosis Lung Disease","volume":"20","author":"Oakland","year":"2012","journal-title":"Mol. Ther."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.addr.2008.09.011","article-title":"Extracellular Barriers in Respiratory Gene Therapy","volume":"61","author":"Sanders","year":"2009","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6014","DOI":"10.1128\/JVI.72.7.6014-6023.1998","article-title":"Limited Entry of Adenovirus Vectors into Well-Differentiated Airway Epithelium Is Responsible for Inefficient Gene Transfer","volume":"72","author":"Pickles","year":"1998","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1650","DOI":"10.1164\/ajrccm\/140.6.1650","article-title":"Immunohistopathologic Localization of Pseudomonas Aeruginosa in Lungs from Patients with Cystic Fibrosis. Implications for the Pathogenesis of Progressive Lung Deterioration","volume":"140","author":"Baltimore","year":"1989","journal-title":"Am. Rev. Respir. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1172\/JCI0213870","article-title":"Effects of Reduced Mucus Oxygen Concentration in Airway Pseudomonas Infections of Cystic Fibrosis Patients","volume":"109","author":"Worlitzsch","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2591","DOI":"10.1016\/j.biomaterials.2008.12.076","article-title":"The Penetration of Fresh Undiluted Sputum Expectorated by Cystic Fibrosis Patients by Non-Adhesive Polymer Nanoparticles","volume":"30","author":"Suk","year":"2009","journal-title":"Biomaterials"},{"key":"ref_63","first-page":"919","article-title":"Actin Filaments Mediate DNA Fiber Formation in Chronic Inflammatory Airway Disease","volume":"148","author":"Sheils","year":"1996","journal-title":"Am. J. Pathol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1183\/09031936.93.03010019","article-title":"The Origin of DNA Associated with Mucus Glycoproteins in Cystic Fibrosis Sputum","volume":"3","author":"Lethem","year":"1990","journal-title":"Eur. Respir. J."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"10219","DOI":"10.1074\/jbc.274.15.10219","article-title":"Basolateral Localization of Fiber Receptors Limits Adenovirus Infection from the Apical Surface of Airway Epithelia","volume":"274","author":"Walters","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"6050","DOI":"10.1128\/JVI.74.13.6050-6057.2000","article-title":"Retargeting the Coxsackievirus and Adenovirus Receptor to the Apical Surface of Polarized Epithelial Cells Reveals the Glycocalyx as a Barrier to Adenovirus-Mediated Gene Transfer","volume":"74","author":"Pickles","year":"2000","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1242\/dmm.006031","article-title":"Airway Basal Stem Cells: A Perspective on Their Roles in Epithelial Homeostasis and Remodeling","volume":"3","author":"Rock","year":"2010","journal-title":"Dis. Model. Mech."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1089\/10430340152712719","article-title":"A Pilot Study of in Vivo Liver-Directed Gene Transfer with an Adenoviral Vector in Partial Ornithine Transcarbamylase Deficiency","volume":"13","author":"Raper","year":"2002","journal-title":"Hum. Gene Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1074\/jbc.271.7.3639","article-title":"Prolonged Metabolic Correction in Adult Ornithine Transcarbamylase-Deficient Mice with Adenoviral Vectors","volume":"271","author":"Ye","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1089\/hum.1998.9.5-671","article-title":"Selective Gene Transfer into the Liver of Non-Human Primates with E1-Deleted, E2A-Defective, or E1-E4 Deleted Recombinant Adenoviruses","volume":"9","author":"Raper","year":"1998","journal-title":"Hum. Gene Ther."},{"key":"ref_71","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_72","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1038\/sj.gt.3301030","article-title":"Expression of Coxsackie Adenovirus Receptor and Alphav-Integrin Does Not Correlate with Adenovector Targeting in Vivo Indicating Anatomical Vector Barriers","volume":"6","author":"Fechner","year":"1999","journal-title":"Gene Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1158\/1541-7786.MCR-13-0244","article-title":"Cancer Gene Discovery: Exploiting Insertional Mutagenesis","volume":"11","author":"Ranzani","year":"2013","journal-title":"Mol. Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.hoc.2017.06.007","article-title":"Nonintegrating Gene Therapy Vectors","volume":"31","author":"Athanasopoulos","year":"2017","journal-title":"Hematol. Oncol. Clin. N. Am."},{"key":"ref_75","first-page":"49","article-title":"Targeting Cell-Specific Gene Expression with an Adenovirus Vector Containing the LacZ Gene under the Control of the CFTR Promoter","volume":"3","author":"Imler","year":"1996","journal-title":"Gene Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/S1525-0016(03)00059-5","article-title":"Reduced Inflammation and Improved Airway Expression Using Helper-Dependent Adenoviral Vectors with a K18 Promoter","volume":"7","author":"Toietta","year":"2003","journal-title":"Mol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1089\/10430349950017455","article-title":"Use of a Liver-Specific Promoter Reduces Immune Response to the Transgene in Adenoviral Vectors","volume":"10","author":"Pastore","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/hum.2009.056","article-title":"Adenovirus 5-Fiber 35 Chimeric Vector Mediates Efficient Apical Correction of the Cystic Fibrosis Transmembrane Conductance Regulator Defect in Cystic Fibrosis Primary Airway Epithelia","volume":"21","author":"Granio","year":"2010","journal-title":"Hum. Gene Ther."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8689","DOI":"10.1128\/JVI.73.10.8689-8695.1999","article-title":"A Chimeric Type 2 Adenovirus Vector with a Type 17 Fiber Enhances Gene Transfer to Human Airway Epithelia","volume":"73","author":"Zabner","year":"1999","journal-title":"J. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/8647","article-title":"A System for the Propagation of Adenoviral Vectors with Genetically Modified Receptor Specificities","volume":"17","author":"Douglas","year":"1999","journal-title":"Nat. Biotechnol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1172\/JCI8858","article-title":"Targeting the Urokinase Plasminogen Activator Receptor Enhances Gene Transfer to Human Airway Epithelia","volume":"105","author":"Drapkin","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1172\/JCI5309","article-title":"CAR-Dependent and CAR-Independent Pathways of Adenovirus Vector-Mediated Gene Transfer and Expression in Human Fibroblasts","volume":"103","author":"Hidaka","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3452","DOI":"10.1128\/JVI.76.7.3452-3460.2002","article-title":"Adenovirus Binding to the Coxsackievirus and Adenovirus Receptor or Integrins Is Not Required to Elicit Brain Inflammation but Is Necessary to Transduce Specific Neural Cell Types","volume":"76","author":"Thomas","year":"2002","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1089\/hgtb.2012.243","article-title":"Pre-Existing Anti-Adeno-Associated Virus Antibodies as a Challenge in AAV Gene Therapy","volume":"24","author":"Joergensen","year":"2013","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"15021","DOI":"10.1038\/mto.2015.21","article-title":"Evaluation of Polymer Shielding for Adenovirus Serotype 6 (Ad6) for Systemic Virotherapy against Human Prostate Cancers","volume":"3","author":"Nguyen","year":"2016","journal-title":"Mol. Ther. Oncolytics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"261","DOI":"10.2174\/138920106777950852","article-title":"Novel Delivery Technologies for Protein and Peptide Therapeutics","volume":"7","author":"Soppimath","year":"2006","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"965","DOI":"10.2165\/00003088-200645100-00002","article-title":"Nanomedicine: Clinical Applications of Polyethylene Glycol Conjugated Proteins and Drugs","volume":"45","author":"Parveen","year":"2006","journal-title":"Clin. Pharmacokinet."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4792","DOI":"10.1128\/JVI.75.10.4792-4801.2001","article-title":"\u201cStealth\u201d Adenoviruses Blunt Cell-Mediated and Humoral Immune Responses against the Virus and Allow for Significant Gene Expression upon Readministration in the Lung","volume":"75","author":"Croyle","year":"2001","journal-title":"J. Virol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1089\/10430349950018021","article-title":"PEGylation of Adenovirus with Retention of Infectivity and Protection from Neutralizing Antibody in Vitro and in Vivo","volume":"10","author":"Lachapelle","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Bandara, R.A., Chen, Z.R., and Hu, J. (2021). Potential of Helper-Dependent Adenoviral Vectors in CRISPR-Cas9-Mediated Lung Gene Therapy. Cell Biosci., 11.","DOI":"10.1186\/s13578-021-00662-w"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Cao, H., Duan, R., and Hu, J. (2020). Overcoming Immunological Challenges to Helper-Dependent Adenoviral Vector-Mediated Long-Term CFTR Expression in Mouse Airways. Genes, 11.","DOI":"10.3390\/genes11050565"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1002\/jgm.797","article-title":"Aerosol Delivery of an Enhanced Helper-Dependent Adenovirus Formulation to Rabbit Lung Using an Intratracheal Catheter","volume":"7","author":"Koehler","year":"2005","journal-title":"J. Gene Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1089\/104303401300042348","article-title":"EGTA Enhancement of Adenovirus-Mediated Gene Transfer to Mouse Tracheal Epithelium in Vivo","volume":"12","author":"Chu","year":"2001","journal-title":"Hum. Gene Ther."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1089\/hum.1998.9.18-2661","article-title":"Enhanced in Vivo Airway Gene Transfer via Transient Modification of Host Barrier Properties with a Surface-Active Agent","volume":"9","author":"Parsons","year":"1998","journal-title":"Hum. Gene Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1089\/104303403765255138","article-title":"Safety and Efficiency of Modulating Paracellular Permeability to Enhance Airway Epithelial Gene Transfer In Vivo","volume":"14","author":"Johnson","year":"2003","journal-title":"Hum. Gene Ther."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1165\/ajrcmb.22.2.3938","article-title":"Increasing Epithelial Junction Permeability Enhances Gene Transfer to Airway Epithelia In Vivo","volume":"22","author":"Wang","year":"2000","journal-title":"Rapid Commun. Am. J. Respir. Cell Mol. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1089\/10430349950018670","article-title":"Delivery of an Adenovirus Vector in a Calcium Phosphate Coprecipitate Enhances the Therapeutic Index of Gene Transfer to Airway Epithelia","volume":"10","author":"Lee","year":"1999","journal-title":"Hum. Gene Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1089\/hum.1998.9.10-1469","article-title":"Potentiation of Gene Transfer to the Mouse Lung by Complexes of Adenovirus Vector and Polycations Improves Therapeutic Potential","volume":"9","author":"Kaplan","year":"1998","journal-title":"Hum. Gene Ther."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/12\/1052\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:52:45Z","timestamp":1760115165000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/13\/12\/1052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,16]]},"references-count":98,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["biology13121052"],"URL":"https:\/\/doi.org\/10.3390\/biology13121052","relation":{},"ISSN":["2079-7737"],"issn-type":[{"value":"2079-7737","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,16]]}}}