CORONA: A Study Using DeltaRex-G Gene Therapy for Symptomatic COVID-19

Summary

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. COVID-19 causes life threatening complications known as Cytokine Release Syndrome or Cytokine Storm and Acute Respiratory Distress Syndrome. These complications are the main causes of death in this global pandemic. Over 1000 clinical trials are on-going worldwide to diagnose, treat, and improve the aggressive clinical course of COVID-19. The investigators propose the first, and so far, only gene therapy solution that has the potential to address this urgent unmet medical need. Rationale 1. There are striking similarities between the damaged lung environment of COVID-19 induced ARDS and the tumor microenvironment (exposed collagen from tissue destruction by invading tumor or by the virus-induced immune response, and presence of activated proliferative cells (cancer cells and tumor associated fibroblasts or activated T cells, macrophages and pulmonary fibroblasts in COVID-19); 2. DeltaRex-G is a disease-seeking retrovector encoding a cytocidal dominant negative human cyclin G1 as genetic payload). When injected intravenously, the DeltaRex-G nanoparticles has a navigational system that targets exposed collagenous proteins (XC proteins) in injured tissues (e.g. inflamed lung, kidney, etc.), thus increasing the effective drug concentration at the sites of injury, in the vicinity of activated/proliferative T cells evoked by COVID-19. Our hypothesis is that DeltaRex-G then enters the rapidly dividing T cells and kills them by arresting the G1cell division cycle, hence, reducing cytokine release and ARDS; 3. Intravenous DeltaRex-G has minimal systemic toxicity due to its navigational system (targeting properties) that limits the biodistribution of DeltaRex-G only to areas of injury where exposed collagenous (XC) proteins are abnormally found; and 4. DeltaRex-G is currently available in FDA approved "Right to Try" or Expanded Access Program for Stage 4 cancers for an intermediate size population. To gain this approval, FDA requires DeltaRex-G to have demonstrated safety and efficacy in early clinical trials.

Timeline

Start

2022-12-12

Primary completion

2023-12-12

Completion

2024-07-12

Outcome

Outcome not reported

Stopped (Business): “Lack of Funding”

Publications

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• Background Chawla SP, Chua VS, Fernandez L, Quon D, Saralou A, Blackwelder WC, Hall FL, Gordon EM. Phase I/II and phase II studies of targeted gene delivery in vivo: intravenous Rexin-G for chemotherapy-resistant sarcoma and osteosarcoma. Mol Ther. 2009 Sep;17(9):1651-7. doi: 10.1038/mt.2009.126. Epub 2009 Jun 16.
• Background Gordon EM, Zhu NL, Forney Prescott M, Chen ZH, Anderson WF, Hall FL. Lesion-targeted injectable vectors for vascular restenosis. Hum Gene Ther. 2001 Jul 1;12(10):1277-87. doi: 10.1089/104303401750270931.
• Background Chawla SP, Bruckner H, Morse MA, Assudani N, Hall FL, Gordon EM. A Phase I-II Study Using Rexin-G Tumor-Targeted Retrovector Encoding a Dominant-Negative Cyclin G1 Inhibitor for Advanced Pancreatic Cancer. Mol Ther Oncolytics. 2018 Dec 14;12:56-67. doi: 10.1016/j.omto.2018.12.005. eCollection 2019 Mar 29.
• Background Gordon EM, Hall FL. Rexin-G, a targeted genetic medicine for cancer. Expert Opin Biol Ther. 2010 May;10(5):819-32. doi: 10.1517/14712598.2010.481666.
• Background Hall FL, Gordon EM, Wu L, Zhu NL, Skotzko MJ, Starnes VA, Anderson WF. Targeting retroviral vectors to vascular lesions by genetic engineering of the MoMLV gp70 envelope protein. Hum Gene Ther. 1997 Dec 10;8(18):2183-92. doi: 10.1089/hum.1997.8.18-2183.
• Background Wu L, Liu L, Yee A, Carbonarohall D, Tolo V, Hall F. Molecular-cloning of the human cycg1 gene encoding a g-type cyclin - overexpression in human osteosarcoma cells. Oncol Rep. 1994 Jul;1(4):705-11. doi: 10.3892/or.1.4.705.
• Background Xu F, Prescott MF, Liu PX, Chen ZH, Liau G, Gordon EM, Hall FL. Long term inhibition of neointima formation in balloon-injured rat arteries by intraluminal instillation of a matrix-targeted retroviral vector bearing a cytocidal mutant cyclin G1 construct. Int J Mol Med. 2001 Jul;8(1):19-30. doi: 10.3892/ijmm.8.1.19.
• Background Zhu NL, Wu L, Liu PX, Gordon EM, Anderson WF, Starnes VA, Hall FL. Downregulation of cyclin G1 expression by retrovirus-mediated antisense gene transfer inhibits vascular smooth muscle cell proliferation and neointima formation. Circulation. 1997 Jul 15;96(2):628-35. doi: 10.1161/01.cir.96.2.628.
• Background Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
• Background Wu KJ, Yee A, Zhu NL, Gordon EM, Hall FL. Characterization of differential gene expression in monkey arterial neointima following balloon catheter injury. Int J Mol Med. 2000 Oct;6(4):433-40.
• Background Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, Muller MA, Drosten C, Pohlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 Mar 5.

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