RAMOT at Tel Aviv University Ltd.

Zymoxins, HCV NS3 protease-activated chimeric toxins:a novel antiviral therapy for the treatment of HCV infections

Posted by RAMOT at Tel Aviv University Ltd.Responsive · Innovative Products and Technologies · Israel

Summary of the technology

Rationally designed viral-protease activated chimeric toxins were developed (“Zymoxins”). The chimeric toxins were constructed by fusing diphtheria toxin A (DTA) or Ricin A chain (RTA), to an inhibitor peptide/domain (defensin for DTA; ribosome stalk peptide for RTS) via an HCV NS3 protease-cleavable linker, thus converting a constitutively active toxin to an HCV NS3 protease-activatable form. The HCV NS3 protease is a virally encoded protease which expression and activity in infected cells is essential for viral replication/maturation. Thus these zymoxins are activated in HCV infected cells which specifically express HCV NS3 protease. In addition, the Zymoxins were fused to the binding and translocation domain of Pseudomonas exotoxin A (PE) for efficient delivery to the cell cytosol, where the toxins inactivate elongation factor 2 (DTA) or inactivate ribosomes (RTA) and cause cell death. For increased specificity, the non-specific cell binding domain I of PE can be replaced with target-specific antibodies.



Project ID : 2-2011-177

Description of the technology

The Technology

 

Rationally designed viral-protease activated chimeric toxins were developed (“Zymoxins”). The chimeric toxins were constructed by fusing diphtheria toxin A (DTA) or Ricin A chain (RTA), to an inhibitor peptide/domain (defensin for DTA; ribosome stalk peptide for RTS) via an HCV NS3 protease-cleavable linker, thus converting a constitutively active toxin to an HCV NS3 protease-activatable form.   The HCV NS3 protease is a virally encoded protease which expression and activity in infected cells is essential for viral replication/maturation. Thus these zymoxins are activated in HCV infected cells which specifically express HCV NS3 protease.   In addition, the Zymoxins were fused to the binding and translocation domain of Pseudomonas exotoxin A (PE) for efficient delivery to the cell cytosol, where the toxins inactivate elongation factor 2 (DTA) or inactivate ribosomes (RTA) and cause cell death. For increased specificity, the non-specific cell binding domain I of PE can be replaced with target-specific antibodies. 

Target population:

         Newly infected patients

         HCV patients undergoing liver transplantation 

Data-to-date

 

The Zymoxins demonstrated specific and efficient cytotoxicity to 293 cells that inducibly express the NS3 protease and to HCV infected hepatome cells and in the HCVcc model, in which recombinant infectious HCV particles are produced in cell culture based on the Huh7.5 hepatoma cell line. 

Patent

PCT/IL2011/000680

Project manager

Adi Elkeles
BD Manager

Project researchers

Itai Benhar
T.A.U Tel Aviv University, Life Sciences
Molecular Microbiology-Biotechnology

Ran TUR-KASPA
T.A.U Tel Aviv University, Medicine-Sackler Faculty
Felsenstein Medical Res Center-Beilinson

Related keywords

  • Biological Sciences
  • Biology / Biotechnology
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  • Industrial Biotechnology
  • Biobased Materials related to Industrial Biotechnology
  • Micro- and Nanotechnology related to Biological sciences
  • Cellular and Molecular Biology Market
  • Agro and Marine biotech
  • Life Sciences and Biotechnology
  • Peptides / Proteins
  • Pharmaceuticals Indications
  • Infection Diseases

About RAMOT at Tel Aviv University Ltd.

Technology Transfer Office from Israel

Ramot is Tel Aviv University's (TAU) technology transfer company and its liaison to industry, bringing promising scientific discoveries made at

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