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Viral gene therapy enables targeted delivery of therapeutic transgenes and represents an attractive platform for tackling acquired and inherited cardiovascular diseases in the future. Current cardiovascular gene therapy trials in humans mainly focus on improving cardiac angiogenesis and function. Encouragingly, local delivery of therapeutic transgenes utilising first-generation human adenovirus serotype (HAd)-5 is safe in the short term and has shown some efficacy in drug refractory angina pectoris and heart failure with reduced ejection fraction. Despite this success, systemic delivery of therapeutic HAd-5 vectors targeting cardiovascular tissues and internal organs is limited by negligible gene transfer to target cells, elimination by the immune system, liver sequestration, off-target effects, and episomal degradation. To circumvent these barriers, cardiovascular gene therapy research has focused on determining the safety and efficacy of rare alternative serotypes and\/or genetically engineered adenoviral capsid protein-modified vectors following local or systemic delivery. Pre-clinical studies have identified several vectors including HAd-11, HAd-35, and HAd-20\u201342-42 as promising platforms for local and systemic targeting of vascular endothelial and smooth muscle cells. In the past, clinical gene therapy trials were often restricted by limited scale-up capabilities of gene therapy medicinal products (GTMPs) and lack of regulatory guidance. However, significant improvement of industrial GTMP scale-up and purification, development of novel producer cell lines, and issuing of GTMP regulatory guidance by national regulatory health agencies have addressed many of these challenges, creating a more robust framework for future adenoviral-based cardiovascular gene therapy. In addition, this has enabled the mass roll out of adenovirus vector-based COVID-19 vaccines.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Key messages<\/jats:title>\n                <jats:p><jats:list list-type=\"bullet\">\n                  <jats:list-item>\n                    <jats:p>First-generation HAd-5 vectors are widely used in cardiovascular gene therapy.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>HAd-5-based gene therapy was shown to lead to cardiac angiogenesis and improved function.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Novel HAd vectors may represent promising transgene carriers for systemic delivery.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Novel methods allow industrial scale-up of rare\/genetically altered Ad serotypes.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>National regulatory health agencies have issued guidance on GMP for GTMPs.<\/jats:p>\n                  <\/jats:list-item>\n                <\/jats:list><\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00109-022-02208-0","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T01:04:23Z","timestamp":1653354263000},"page":"875-901","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Adenoviral vectors for cardiovascular gene therapy applications: a clinical and industry perspective"],"prefix":"10.1007","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3829-8693","authenticated-orcid":false,"given":"Schwartze","family":"JT","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4094-6362","authenticated-orcid":false,"given":"Havenga","family":"M","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8731-6689","authenticated-orcid":false,"given":"Bakker","family":"WAM","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3711-6547","authenticated-orcid":false,"given":"Bradshaw","family":"AC","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9691-6210","authenticated-orcid":false,"given":"Nicklin","family":"SA","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"2208_CR1","doi-asserted-by":"publisher","unstructured":"Blencowe H et al (2018) Rare single gene disorders: estimating baseline prevalence and outcomes worldwide.\u00a0J Community Genet 9(4):397\u2013406.\u00a0https:\/\/doi.org\/10.1007\/s12687-018-0376-2","DOI":"10.1007\/s12687-018-0376-2"},{"key":"2208_CR2","doi-asserted-by":"publisher","unstructured":"Hammond HK et al (2016) Intracoronary gene transfer of adenylyl cyclase 6 in patients with heart failure: a randomized clinical trial.\u00a0JAMA Cardiol 1(2):163\u201371.\u00a0https:\/\/doi.org\/10.1001\/jamacardio.2016.0008","DOI":"10.1001\/jamacardio.2016.0008"},{"key":"2208_CR3","doi-asserted-by":"publisher","unstructured":"Greenberg B et al (2016) Calcium upregulation by percutaneous administration of gene therapy in patients with cardiac disease (CUPID 2): a randomised, multinational, double-blind, placebo-controlled, phase 2b trial.\u00a0Lancet 387 (10024):1178\u201386.\u00a0https:\/\/doi.org\/10.1016\/S0140-6736(16)00082-9","DOI":"10.1016\/S0140-6736(16)00082-9"},{"key":"2208_CR4","doi-asserted-by":"publisher","unstructured":"Feng F, Harper RL, Reynolds PN (2016) BMPR2 gene delivery reduces mutation-related PAH and counteracts TGF-\u03b2-mediated pulmonary cell signalling.\u00a0Respirology 21(3):526\u201332.\u00a0https:\/\/doi.org\/10.1111\/resp.12712","DOI":"10.1111\/resp.12712"},{"key":"2208_CR5","doi-asserted-by":"publisher","unstructured":"Jaffe HA et al (1992) Adenovirus-mediated in vivo gene transfer and expression in normal rat liver. 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