Safety and biodistribution of XC001 (encoberminogene rezmadenovec) gene therapy in rats: a potential therapy for cardiovascular diseases

Henry TD, Satran D, Hodges JS, Johnson RK, Poulose AK, Campbell AR, et al. Long-term survival in patients with refractory angina. Eur Heart J. 2013;34:2683–8.

Article  PubMed  Google Scholar 

Cheng K, de Silva R. New advances in the management of refractory angina pectoris. Eur Cardiol. 2018;13:70–9.

Article  PubMed  PubMed Central  Google Scholar 

Krock BL, Skuli N, Celeste Simon M. Hypoxia-Induced Angiogenesis: Good and Evil. Genes Cancer. 2011;2:1117–33.

Article  PubMed  PubMed Central  Google Scholar 

Wold WSM, Ison MG. Adenoviruses. In: Fields BN, Knipe DM and Howley PM (eds). Fields Virology, Vol 1. 6th ed. Lippincott Williams & Wilkins, Philadelphia, 2013. pp 1732–67.

Ylä-Herttuala S, Baker AH. Cardiovascular gene therapy: past, present, and future. Mol Ther. 2017;25:1095–106.

Article  PubMed  PubMed Central  Google Scholar 

Povsic TJ, Henry TD, Ohman EM, Pepine CJ, Crystal RG, Reinhardt RR, et al. Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (The EXACT Trial): Rationale, Design, and Clinical Considerations. Am Heart J. 2021;241:38–49.

Article  CAS  PubMed  Google Scholar 

Guzman RJ, Lemarchand P, Crystal RG, Epstein SE, Finkel T. Efficient gene transfer into myocardium by direct injection of adenovirus vectors. Circ Res. 1993;73:1202–7.

Article  CAS  PubMed  Google Scholar 

Mack CA, Patel SR, Schwarz EA, Zanzonico P, Hahn RT, Ilercil A, et al. Biologic bypass with the use of adenovirus-mediated gene transfer of the complementary deoxyribonucleic acid for vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart. J Thorac Cardiovasc Surg. 1998;115:168–76.

Article  CAS  PubMed  PubMed Central  Google Scholar 

French BA, Mazur W, Geske RS, Bolli R. Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors. Circulation. 1994;90:2414–24.

Article  CAS  PubMed  Google Scholar 

Yuan B, Zhao Z, Zhang YR, Wu CT, Jin WG, Zhao S, et al. Short-term safety and curative effect of recombinant adenovirus carrying hepatocyte growth factor gene on ischemic cardiac disease. In Vivo. 2008;22:629–32.

CAS  PubMed  Google Scholar 

Vassalli G, Bueler H, Dudler J, von Segesser LK, Kappenberger L. Adeno-associated virus (AAV) vectors achieve prolonged transgene expression in mouse myocardium and arteries in vivo: a comparative study with adenovirus vectors. Int J Cardiol. 2003;90:229–38.

Article  PubMed  Google Scholar 

Jones JM, Koch WJ. Gene therapy approaches to cardiovascular disease. Methods Mol Med. 2005;112:15–35.

CAS  PubMed  Google Scholar 

Nayak L, Rosengart TK. Gene therapy for heart failure. Semin Thorac Cardiovasc Surg. 2005;17:343–7.

Article  PubMed  Google Scholar 

Zhang D, Gai L, Fan R, Dong W, Wen Y. Efficacy and safety of therapeutic angiogenesis from direct myocardial administration of an adenoviral vector expressing vascular endothelial growth factor 165. Chinese Med J. 2002;115:643–8.

CAS  Google Scholar 

Whitlock PR, Hackett NR, Leopold PL, Rosengart TK, Crystal RG. Adenovirus-mediated transfer of a mini gene expressing multiple isoforms of VEGF is more effective at inducing angiogenesis than comparable vectors expressing individual VEGF cDNAs. Mol Ther. 2004;9:67–75.

Article  CAS  PubMed  Google Scholar 

Stewart DJ, Hilton JD, Arnold JM, Gregoire J, Rivard A, Archer SL, et al. Angiogenic gene therapy in patients with nonrevascularizable ischemic heart disease: a phase 2 randomized, controlled trial of AdVEGF(121) (AdVEGF121) versus maximum medical treatment. Gene Ther. 2006;13:1503–11.

Article  CAS  PubMed  Google Scholar 

Amano H, Hackett NR, Kaner RJ, Whitlock P, Rosengart TK, Crystal RG. Alteration of splicing signals in a genomic/cDNA hybrid VEGF gene to modify the ratio of expressed VEGF isoforms enhances safety of angiogenic gene therapy. Mol Ther. 2005;2:716–24.

Article  Google Scholar 

Kaminsky SM, Quach L, Chen S, Pierre-Destine L, Van de Graaf B, Monette S, et al. Safety of direct cardiac administration of AdVEGF-All6A+, a replication-deficient adenovirus vector cDNA/genomic hybrid expressing all three major isoforms of human vascular endothelial growth factor to the ischemic myocardium of rats. Human Gene Ther Clin Dev. 2013;24:38–46.

Article  CAS  Google Scholar 

Schafer KA, Eighmy J, Fikes JD, Halpern WG, Hukkanen RR, Long GG, et al. Use of Severity Grades to Characterize Histopathologic Changes. Toxicol Pathol. 2018;46:256–65.

Article  CAS  PubMed  Google Scholar 

Thierry AR, Lunardi-Iskandar Y, Bryant JL, Rabinovinch P, Gallo RC, Mahan LC. Systemic gene therapy: biodistribution and long-term expression of a transgene in mice. Proc Natl Acad Sci USA. 1995;92:9742–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schrader C, Schielke A, Ellerbroek L, Johne R. PCR inhibitors- occurrence, properties, and removal. J Appl Microbiol. 2012;113:1014–26.

Article  CAS  PubMed  Google Scholar 

Povsic TJ, Traverse JH, Henry TD, Rosengart TK, Crystal RG, Dittrich HC et al. Preliminary Safety, Tolerability and Efficacy of Direct Epicardial Administration of Encoberminogene Rezmadenovec to Ischemic Myocardium in Patients with Refractory Angina: Six Month Phase 1 Data. Abstract presented at: 2022 American Society of Gene and Cell Therapy Annual Meeting; Washington, DC. 2022;May.

Machitani M, Yamaguchi T, Shimizu K, Shimizu K, Sakurai F, Katayama K, et al. Adenovirus vector-derived VA-RNA-mediated innate immune responses. Pharmaceutics. 2011;3:338–53.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Magovern CJ, Mack CA, Zhang J, Hahn RT, Wilson K, Isom OW, et al. Direct in vivo gene transfer to canine myocardium using a replication-deficient adenovirus vector. Ann Thorac Surg. 1996;62:425–34.

Article  CAS  PubMed  Google Scholar 

Patel SR, Lee LY, Mack CA, Polce DR, El-Sawy T, Hackett NR, et al. Safety of direct myocardial administration of an adenovirus vector encoding vascular endothelial growth factor 121. Hum Gene Ther. 1999;10:1331–48.

Article  CAS  PubMed  Google Scholar 

Perin EC, Silva GV, Assad JAR, Vela D, Buja LM, Sousa ALS, et al. Comparison of intracoronary and transendocardial delivery of allogeneic mesenchymal cells in a canine model of acute myocardial infarction. J Mol Cell Cardiol. 2008;44:486–95.

Article  CAS  PubMed  Google Scholar 

Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, et al. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation. 2013;128:S42–49.

Article  CAS  PubMed  Google Scholar 

Hackett NR, Sawy TE, Lee LY, Silva I, O'Leary J, Rosengart TK, et al. Use of quantitative TaqMan real-time PCR to track the time-dependent distribution of gene transfer vectors in vivo. Mol Ther. 2000;2:649–56.

Article  CAS  PubMed  Google Scholar 

Rosengart TK, Lee LY, Patel SR, Sanborn TA, Parikh M, Bergman GW, et al. Angiogenesis gene therapy: phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation. 1999;100:468–74.

Article  CAS  PubMed  Google Scholar 

Lee CS, Bishop ES, Zhang R, Yu X, Farina EM, Yan S, et al. Adenovirus-mediated gene delivery: potential applications for gene and cell-based therapies in the new era of personalized medicine. Genes Dis. 2017;4:43–63.

Article  PubMed  PubMed Central  Google Scholar 

Comments (0)

No login
gif