{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T09:30:22Z","timestamp":1790847022947,"version":"4.1.0"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011352","name":"Center for Gene Therapy, University of Iowa","doi-asserted-by":"publisher","award":["UG3 HL147366 P01 HL51670 P01 HL091842 P01 HL152960 DK54759"],"award-info":[{"award-number":["UG3 HL147366 P01 HL51670 P01 HL091842 P01 HL152960 DK54759"]}],"id":[{"id":"10.13039\/100011352","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genome Ed."],"abstract":"<jats:p>Pulmonary surfactant is critically important to prevent atelectasis by lowering the surface tension of the alveolar lining liquid. While respiratory distress syndrome (RDS) is common in premature infants, severe RDS in term and late preterm infants suggests an underlying genetic etiology. Pathogenic variants in the genes encoding key components of pulmonary surfactant including surfactant protein B (SP-B, <jats:italic>SFTPB<\/jats:italic> gene), surfactant protein C (SP-C, <jats:italic>SFTPC<\/jats:italic> gene), and the ATP-Binding Cassette transporter A3 (ABCA3, <jats:italic>ABCA3<\/jats:italic> gene) result in severe neonatal RDS or childhood interstitial lung disease (chILD). These proteins play essential roles in pulmonary surfactant biogenesis and are expressed in alveolar epithelial type II cells (AEC2), the progenitor cell of the alveolar epithelium. SP-B deficiency most commonly presents in the neonatal period with severe RDS and requires lung transplantation for survival. <jats:italic>SFTPC<\/jats:italic> mutations act in an autosomal dominant fashion and more commonly presents with chILD or idiopathic pulmonary fibrosis than neonatal RDS. ABCA3 deficiency often presents as neonatal RDS or chILD. Gene therapy is a promising option to treat monogenic lung diseases. Successes and challenges in developing gene therapies for genetic disorders of surfactant dysfunction include viral vector design and tropism for target cell types. In this review, we explore adeno-associated virus (AAV), lentiviral, and adenoviral (Ad)-based vectors as delivery vehicles. Both gene addition and gene editing strategies are compared to best design treatments for lung diseases resulting from pathogenic variants in the <jats:italic>SFTPB, SFTPC,<\/jats:italic> and <jats:italic>ABCA3<\/jats:italic> genes<jats:italic>.<\/jats:italic><\/jats:p>","DOI":"10.3389\/fgeed.2021.785829","type":"journal-article","created":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T05:56:15Z","timestamp":1642139775000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":33,"title":["Gene Therapy Potential for Genetic Disorders of Surfactant Dysfunction"],"prefix":"10.3389","volume":"3","author":[{"given":"Ashley L.","family":"Cooney","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Wambach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick L.","family":"Sinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Paul B.","family":"McCray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1016\/j.bbalip.2012.09.010","article-title":"Surfactant Phospholipid Metabolism","volume":"1831","author":"Agassandian","year":"2013","journal-title":"Biochim. Biophys. Acta (Bba) - Mol. Cel Biol. Lipids"},{"key":"B2","doi-asserted-by":"publisher","first-page":"9640","DOI":"10.1074\/jbc.272.15.9640","article-title":"Rescue of SP-B Knockout Mice with a Truncated SP-B Proprotein","volume":"272","author":"Akinbi","year":"1997","journal-title":"J. Biol. Chem."},{"key":"B3","doi-asserted-by":"publisher","first-page":"eaav8375","DOI":"10.1126\/scitranslmed.aav8375","article-title":"In Utero gene Editing for Monogenic Lung Disease","volume":"11","author":"Alapati","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"9628","DOI":"10.1074\/jbc.M611767200","article-title":"Abca3 as a Lipid Transporter in Pulmonary Surfactant Biogenesis","volume":"282","author":"Ban","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1177\/1535370217713000","article-title":"Featured Article: Electroporation-Mediated Gene Delivery of Surfactant Protein B (Sp-b) Restores Expression and Improves Survival in Mouse Model of Sp-B Deficiency","volume":"242","author":"Barnett","year":"2017","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e0161072","DOI":"10.1371\/journal.pone.0161072","article-title":"Targeted Integration of a Super-Exon into the Cftr Locus Leads to Functional Correction of a Cystic Fibrosis Cell Line Model","volume":"11","author":"Bednarski","year":"2016","journal-title":"PLoS One"},{"key":"B7","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1007\/s00441-016-2554-z","article-title":"The Biology of the Abca3 Lipid Transporter in Lung Health and Disease","volume":"367","author":"Beers","year":"2017","journal-title":"Cell Tissue Res"},{"key":"B8","doi-asserted-by":"publisher","first-page":"L646","DOI":"10.1152\/ajplung.00409.2009","article-title":"Conditional Deletion ofAbca3in Alveolar Type II Cells Alters Surfactant Homeostasis in Newborn and Adult Mice","volume":"298","author":"Besnard","year":"2010","journal-title":"Am. J. Physiology-Lung Cell Mol. Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e337","DOI":"10.1038\/mtna.2016.44","article-title":"A High-Capacity Adenoviral Hybrid Vector System Utilizing the Hyperactive Sleeping beauty Transposase Sb100x for Enhanced Integration","volume":"5","author":"Boehme","year":"2016","journal-title":"Mol. Ther. - Nucleic Acids"},{"key":"B10","doi-asserted-by":"publisher","first-page":"11747","DOI":"10.1128\/JVI.75.23.11747-11754.2001","article-title":"Vesicular Stomatitis Virus G-Pseudotyped Lentivirus Vectors Mediate Efficient Apical Transduction of Polarized Quiescent Primary Alveolar Epithelial Cells","volume":"75","author":"Borok","year":"2001","journal-title":"J. Virol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1089\/hum.2020.138","article-title":"Adeno-Associated Virus-Based Gene Therapy for Lifelong Correction of Genetic Disease","volume":"31","author":"Brommel","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"B12","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jpeds.2004.10.028","article-title":"A Common Mutation in the Surfactant Protein C Gene Associated with Lung Disease","volume":"146","author":"Cameron","year":"2005","journal-title":"J. Pediatr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"3708","DOI":"10.3390\/ijms21103708","article-title":"Lipid-Protein and Protein-Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis","volume":"21","author":"Ca\u00f1adas","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"7794","DOI":"10.1073\/pnas.92.17.7794","article-title":"Targeted Disruption of the Surfactant Protein B Gene Disrupts Surfactant Homeostasis, Causing Respiratory Failure in Newborn Mice","volume":"92","author":"Clark","year":"1995","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1126\/science.1948032","article-title":"Pulmonary Surfactant Protein B (Sp-b): Structure-Function Relationships","volume":"254","author":"Cochrane","year":"1991","journal-title":"Science"},{"key":"B16","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1038\/mt.2014.254","article-title":"Hybrid Nonviral\/Viral Vector Systems for Improved Piggybac DNA Transposon In Vivo Delivery","volume":"23","author":"Cooney","year":"2015","journal-title":"Mol. Ther."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1038\/sj.gt.3301301","article-title":"Production of First Generation Adenovirus Vectors: A Review","volume":"7","author":"Danthinne","year":"2000","journal-title":"Gene Ther."},{"key":"B18","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/gt.2009.166","article-title":"The Sp-C Promoter Facilitates Alveolar Type Ii Epithelial Cell-Specific Plasmid Nuclear Import and Gene Expression","volume":"17","author":"Degiulio","year":"2010","journal-title":"Gene Ther."},{"key":"B19","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/ped4.12020","article-title":"The Classification of Atp-Binding Cassette Subfamily a Member 3 Mutations Using the Cystic Fibrosis Transmembrane Conductance Regulator Classification System","volume":"2","author":"Denman","year":"2018","journal-title":"Pediatr. Invest."},{"key":"B20","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1089\/hum.2018.012","article-title":"Micro-Dystrophin Gene Therapy Goes Systemic in Duchenne Muscular Dystrophy Patients","volume":"29","author":"Duan","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1203\/00006450-200009000-00003","article-title":"Prolonged Survival in Hereditary Surfactant Protein B (Sp-b) Deficiency Associated with a Novel Splicing Mutation","volume":"48","author":"Dunbar","year":"2000","journal-title":"Pediatr. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.jpeds.2017.01.017","article-title":"Outcomes of Lung Transplantation for Infants and Children with Genetic Disorders of Surfactant Metabolism","volume":"184","author":"Eldridge","year":"2017","journal-title":"J. Pediatr."},{"key":"B23","doi-asserted-by":"publisher","first-page":"4306","DOI":"10.1016\/j.febslet.2010.09.026","article-title":"The Surfactant Lipid Transporter Abca3 Is N-Terminally Cleaved inside Lamp3-Positive Vesicles","volume":"584","author":"Engelbrecht","year":"2010","journal-title":"FEBS Lett."},{"key":"B24","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/rr36","article-title":"Alveolar Epithelial Type Ii Cell: Defender of the Alveolus Revisited","volume":"2","author":"Fehrenbach","year":"2001","journal-title":"Respir. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1194\/jlr.M600449-JLR200","article-title":"Abca3 Inactivation in Mice Causes Respiratory Failure, Loss of Pulmonary Surfactant, and Depletion of Lung Phosphatidylglycerol","volume":"48","author":"Fitzgerald","year":"2007","journal-title":"J. Lipid Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1203\/01.pdr.0000219311.14291.df","article-title":"Surfactant Composition and Function in Patients with Abca3 Mutations","volume":"59","author":"Garmany","year":"2006","journal-title":"Pediatr. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1203\/PDR.0b013e31816fdbeb","article-title":"Population and Disease-Based Prevalence of the Common Mutations Associated with Surfactant Deficiency","volume":"63","author":"Garmany","year":"2008","journal-title":"Pediatr. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"6366","DOI":"10.1073\/pnas.101500298","article-title":"Altered Stability of Pulmonary Surfactant in Sp-C-Deficient Mice","volume":"98","author":"Glasser","year":"2001","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"L64","DOI":"10.1152\/ajplung.90640.2008","article-title":"Surfactant Protein C-Deficient Mice Are Susceptible to Respiratory Syncytial Virus Infection","volume":"297","author":"Glasser","year":"2009","journal-title":"Am. J. Physiology-Lung Cell Mol. Physiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1164\/rccm.201206-1056OC","article-title":"Assessment of F\/hn-Pseudotyped Lentivirus as a Clinically Relevant Vector for Lung Gene Therapy","volume":"186","author":"Griesenbach","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1053\/j.semperi.2008.08.003","article-title":"Posttranslational Regulation of Surfactant Protein B Expression","volume":"32","author":"Guttentag","year":"2008","journal-title":"Semin. Perinatology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1298","DOI":"10.1002\/humu.24014","article-title":"Functional Characterization of Four ATP\u2010Binding Cassette Transporter A3 Gene ( ABCA3 ) Variants","volume":"41","author":"Hu","year":"2020","journal-title":"Hum. Mutat."},{"key":"B33","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.ymthe.2006.03.014","article-title":"Robust Systemic Transduction with Aav9 Vectors in Mice: Efficient Global Cardiac Gene Transfer superior to that of Aav8","volume":"14","author":"Inagaki","year":"2006","journal-title":"Mol. Ther."},{"key":"B34","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.stem.2017.08.014","article-title":"Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells","volume":"21","author":"Jacob","year":"2017","journal-title":"Cell Stem Cell"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3303","DOI":"10.1038\/s41596-019-0220-0","article-title":"Derivation of Self-Renewing Lung Alveolar Epithelial Type Ii Cells from Human Pluripotent Stem Cells","volume":"14","author":"Jacob","year":"2019","journal-title":"Nat. Protoc."},{"key":"B36","doi-asserted-by":"publisher","first-page":"3929","DOI":"10.1038\/s41467-020-17577-8","article-title":"A Lung Tropic Aav Vector Improves Survival in a Mouse Model of Surfactant B Deficiency","volume":"11","author":"Kang","year":"2020","journal-title":"Nat. Commun."},{"key":"B37","doi-asserted-by":"publisher","first-page":"e126125","DOI":"10.1172\/jci.insight.126125","article-title":"A Sftpc Brichos Mutant Links Epithelial ER Stress and Spontaneous Lung Fibrosis","volume":"4","author":"Katzen","year":"2019","journal-title":"JCI Insight"},{"key":"B38","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1097\/MCP.0000000000000680","article-title":"Abca3 Mutations in Adult Pulmonary Fibrosis Patients: A Case Series and Review of Literature","volume":"26","author":"Klay","year":"2020","journal-title":"Curr. Opin. Pulm. Med."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1056\/NEJMoa2027675","article-title":"Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency","volume":"384","author":"Kohn","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2153","DOI":"10.12688\/f1000research.11243.1","article-title":"In Vivo Genome Editing in Animals Using Aav-Crispr System: Applications to Translational Research of Human Disease","volume":"6","author":"Lau","year":"2017","journal-title":"F1000Res"},{"key":"B41","doi-asserted-by":"publisher","first-page":"13450","DOI":"10.1038\/s41598-019-49696-8","article-title":"Reversal of Surfactant Protein B Deficiency in Patient Specific Human Induced Pluripotent Stem Cell Derived Lung Organoids by Gene Therapy","volume":"9","author":"Leibel","year":"2019","journal-title":"Sci. Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41551-019-0501-5","article-title":"Cytosine and Adenine Base Editing of the Brain, Liver, Retina, Heart and Skeletal Muscle of Mice via Adeno-Associated Viruses","volume":"4","author":"Levy","year":"2020","journal-title":"Nat. Biomed. Eng."},{"key":"B43","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1034\/j.1399-0004.2000.580305.x","article-title":"Polymorphisms of humanSP-A,SP-B, andSP-Dgenes: Association ofSP-BThr131Ile with ARDS","volume":"58","author":"Lin","year":"2000","journal-title":"Clin. Genet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1164\/rccm.201411-1955LE","article-title":"Chronic Ventilation in Infants with Surfactant Protein C Mutations: An Alternative to Lung Transplantation","volume":"191","author":"Liptzin","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1056\/NEJMoa0802315","article-title":"Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis","volume":"358","author":"Maguire","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"B46","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1038\/nbt.3241","article-title":"In Vivo Genome Editing Using Nuclease-Encoding mRNA Corrects SP-B Deficiency","volume":"33","author":"Mahiny","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.3390\/pharmaceutics12111051","article-title":"Large-Scale Production of Lentiviral Vectors: Current Perspectives and Challenges","volume":"12","author":"Mart\u00ednez-Molina","year":"2020","journal-title":"Pharmaceutics"},{"key":"B48","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1164\/arrd.1977.115.S.81","article-title":"Type Ii Alveolar Cell. Defender of the Alveolus","volume":"115","author":"Mason","year":"1977","journal-title":"Am. Rev. Respir. Dis."},{"key":"B49","doi-asserted-by":"publisher","first-page":"34503","DOI":"10.1074\/jbc.M600071200","article-title":"Characterization and Classification of Atp-Binding Cassette Transporter Abca3 Mutants in Fatal Surfactant Deficiency","volume":"281","author":"Matsumura","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1186\/s13287-020-01950-x","article-title":"Identification of Aav Serotypes for Lung Gene Therapy in Human Embryonic Stem Cell-Derived Lung Organoids","volume":"11","author":"Meyer-Berg","year":"2020","journal-title":"Stem Cel Res Ther"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1038\/s41375-018-0106-0","article-title":"Clinical Use of Lentiviral Vectors","volume":"32","author":"Milone","year":"2018","journal-title":"Leukemia"},{"key":"B53","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1016\/j.omtm.2020.11.013","article-title":"A Human Surfactant B Deficiency Air-Liquid Interface Cell Culture Model Suitable for Gene Therapy Applications","volume":"20","author":"Munis","year":"2021","journal-title":"Mol. Ther. - Methods Clin. Develop."},{"key":"B54","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1016\/s0734-9750(02)00030-7","article-title":"Production of Adenovirus Vector for Gene Therapy","volume":"20","author":"Nadeau","year":"2003","journal-title":"Biotechnol. Adv."},{"key":"B55","doi-asserted-by":"publisher","first-page":"20S","DOI":"10.1378\/chest.121.3_suppl.20s","article-title":"Mutations in the Surfactant Protein C Gene Associated with Interstitial Lung Disease","volume":"121","author":"Nogee","year":"2002","journal-title":"Chest"},{"key":"B56","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1056\/NEJM200102223440805","article-title":"A Mutation in the Surfactant Protein C Gene Associated with Familial Interstitial Lung Disease","volume":"344","author":"Nogee","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"B57","doi-asserted-by":"publisher","first-page":"4008","DOI":"10.1172\/JCI99287","article-title":"Expression of Mutant Sftpc in Murine Alveolar Epithelia Drives Spontaneous Lung Fibrosis","volume":"128","author":"Nureki","year":"2018","journal-title":"J. Clin. Invest."},{"key":"B58","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1038\/s41420-019-0147-9","article-title":"Alveolar Type 2 Progenitor Cells for Lung Injury Repair","volume":"5","author":"Olajuyin","year":"2019","journal-title":"Cel Death Discov."},{"key":"B59","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1513\/pats.200701-018AW","article-title":"Immunomodulatory Roles of Surfactant Proteins a and D: Implications in Lung Disease","volume":"4","author":"Pastva","year":"2007","journal-title":"Proc. Am. Thorac. Soc."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1097\/JOM.0000000000000879","article-title":"Risks Associated with Lentiviral Vector Exposures and Prevention Strategies","volume":"58","author":"Schlimgen","year":"2016","journal-title":"J. Occup. Environ. Med."},{"key":"B61","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1089\/hum.2020.054","article-title":"Detailed Protocol for the Novel and Scalable Viral Vector Upstream Process for Aav Gene Therapy Manufacturing","volume":"32","author":"Selvaraj","year":"2021","journal-title":"Hum. Gene Ther."},{"key":"B62","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.jaci.2019.03.012","article-title":"Lentiviral Gene Therapy Corrects Platelet Phenotype and Function in Patients with Wiskott-Aldrich Syndrome","volume":"144","author":"Sereni","year":"2019","journal-title":"J. Allergy Clin. Immunol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1056\/NEJMoa032178","article-title":"ABCA3Gene Mutations in Newborns with Fatal Surfactant Deficiency","volume":"350","author":"Shulenin","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"10684","DOI":"10.1128\/JVI.00227-08","article-title":"Lentivirus Vector Can Be Readministered to Nasal Epithelia without Blocking Immune Responses","volume":"82","author":"Sinn","year":"2008","journal-title":"J. Virol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1038\/mtna.2012.47","article-title":"Lentiviral Vector Gene Transfer to Porcine Airways","volume":"1","author":"Sinn","year":"2012","journal-title":"Mol. Ther. - Nucleic Acids"},{"key":"B66","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.omtm.2020.10.009","article-title":"Laboratory-Scale Lentiviral Vector Production and Purification for Enhanced Ex Vivo and In Vivo Genetic Engineering","volume":"19","author":"Soldi","year":"2020","journal-title":"Mol. Ther. - Methods Clin. Develop."},{"key":"B67","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1038\/labinvest.3780044","article-title":"Lamellar Body Formation in Normal and Surfactant Protein B-Deficient Fetal Mice","volume":"80","author":"Stahlman","year":"2000","journal-title":"Lab. Invest."},{"key":"B68","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.jconrel.2019.02.009","article-title":"Long-Term Correction of Hemophilia B Using Adenoviral Delivery of Crispr\/cas9","volume":"298","author":"Stephens","year":"2019","journal-title":"J. Controlled Release"},{"key":"B69","doi-asserted-by":"publisher","first-page":"11277","DOI":"10.1073\/pnas.89.23.11277","article-title":"Aerosol Gene Delivery In Vivo","volume":"89","author":"Stribling","year":"1992","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1164\/rccm.200112-123OC","article-title":"Heterozygosity for a Surfactant Protein C Gene Mutation Associated with Usual Interstitial Pneumonitis and Cellular Nonspecific Interstitial Pneumonitis in One Kindred","volume":"165","author":"Thomas","year":"2002","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B71","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1056\/NEJMoa1705342","article-title":"Gene Therapy in Patients with Transfusion-Dependent \u03b2-Thalassemia","volume":"378","author":"Thompson","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B72","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1097\/00000441-200101000-00005","article-title":"Surfactant Protein B Deficiency: Insights into Surfactant Function through Clinical Surfactant Protein Deficiency","volume":"321","author":"Thompson","year":"2001","journal-title":"Am. J. Med. Sci."},{"key":"B73","doi-asserted-by":"publisher","first-page":"L291","DOI":"10.1152\/ajplung.00400.2020","article-title":"The Common ABCA3E292V Variant Disrupts AT2 Cell Quality Control and Increases Susceptibility to Lung Injury and Aberrant Remodeling","volume":"321","author":"Tomer","year":"2021","journal-title":"Am. J. Physiology-Lung Cell Mol. Physiol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"eaav4523","DOI":"10.1126\/scitranslmed.aav4523","article-title":"Intein-Mediated Protein Trans-splicing Expands Adeno-Associated Virus Transfer Capacity in the Retina","volume":"11","author":"Tornabene","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"B75","doi-asserted-by":"publisher","first-page":"30408","DOI":"10.1074\/jbc.M004782200","article-title":"Non-Replicating Epstein-Barr Virus-Based Plasmids Extend Gene Expression and Can Improve Gene Therapy In Vivo","volume":"275","author":"Tu","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B76","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/gt.2017.91","article-title":"Optimization of Lentiviral Vector Production for Scale-Up in Fixed-Bed Bioreactor","volume":"25","author":"Valkama","year":"2018","journal-title":"Gene Ther."},{"key":"B77","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1164\/rccm.201402-0342OC","article-title":"Genotype-phenotype Correlations for Infants and Children with Abca3 Deficiency","volume":"189","author":"Wambach","year":"2014","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"B78","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1165\/rcmb.2016-0008OC","article-title":"Functional Characterization of Atp-Binding Cassette Transporter A3 Mutations from Infants with Respiratory Distress Syndrome","volume":"55","author":"Wambach","year":"2016","journal-title":"Am. J. Respir. Cel Mol Biol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1165\/rcmb.2020-0034MA","article-title":"Functional Genomics of Abca3 Variants","volume":"63","author":"Wambach","year":"2020","journal-title":"Am. J. Respir. Cel Mol Biol"},{"key":"B80","doi-asserted-by":"publisher","first-page":"253","DOI":"10.2350\/09-01-0586.1","article-title":"Genetic Disorders of Surfactant Dysfunction","volume":"12","author":"Wert","year":"2009","journal-title":"Pediatr. Dev. Pathol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"2141","DOI":"10.1056\/NEJMra022387","article-title":"Hydrophobic Surfactant Proteins in Lung Function and Disease","volume":"347","author":"Whitsett","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"B82","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1089\/hum.2015.001","article-title":"Optimization of Recombinant Adeno-Associated Virus-Mediated Expression for Large Transgenes, Using a Synthetic Promoter and Tandem Array Enhancers","volume":"26","author":"Yan","year":"2015","journal-title":"Hum. Gene Ther."}],"container-title":["Frontiers in Genome Editing"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgeed.2021.785829\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T05:56:18Z","timestamp":1642139778000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgeed.2021.785829\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,14]]},"references-count":82,"alternative-id":["10.3389\/fgeed.2021.785829"],"URL":"https:\/\/doi.org\/10.3389\/fgeed.2021.785829","relation":{},"ISSN":["2673-3439"],"issn-type":[{"value":"2673-3439","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,14]]},"article-number":"785829"}}