(against SARS-CoV-2 coronavirus)
"Cell & Gene Therapy" LTD is one of the members of the international group of companies working on innovative DNA-vaccine against SARS-CoV-2 coronavirus on the base of our own DNA-vectors, encoding immunogenic epitopes of SARS-CoV-2 proteins.
Currently, we have created samples of the DNA-vaccine, the bank of producer strains for its development on a commercial scale and completed a package of international patent procedures, performed the initial in vitro and in vivo studies, confirming the efficiency and safety of the DNA-vaccine. Besides, we have prepared process flow documentation of industrial production ensuring acceptable pricing characteristics. At this stage, preclinical studies in animals is being prepared out to evaluate the pharmacological activity and safety of the DNA vaccine.
The Vaccine Development
Current outcomes of the project implementation:
A DNA vaccine has been constructed in the form of a composition of gene therapy DNA vectors based on the gene therapy DNA vector GDTT1.8NAS12 encoding the three most immunogenic epitopes of the SARS-CoV-2 virus proteins - S, M, and N. A distinctive feature of the DNA vaccine is that each of the constructed gene therapy DNA vectors included in the DNA vaccine, due to the limited size of GDTT1.8NAS12 vector part, not exceeding 2600 bp, has the ability to efficiently penetrate into human and animal cells and express the target proteins of the SARS-CoV-2 virus cloned into it. Another difference of the DNA vaccine is that each of the constructed gene therapy DNA vectors included in the DNA vaccine has nucleotide sequences as structural elements, which are not antibiotic resistance genes or regulatory elements of viral genomes, which ensures its safe use for gene therapy and human vaccination.
Producer strains on the basis of Escherichia coli JM110-NAS have been obtained, carrying gene therapy DNA vectors for their development with a possibility of selection without the use of antibiotics when obtaining a gene therapy DNA vector for their inclusion in the DNA vaccine for vaccination of humans against SARS-CoV virus.
A method of production of the DNA vaccine on a commercial scale has been developed in the form of a composition of gene therapy DNA vectors on the base of gene therapy vector GDTT1.8NAS12, encoding the three most immunogenic epitopes of the SARS-CoV-2 virus proteins
Samples of the DNA vaccine in the volume necessary for preclinical studies have been produced.
A bank of producer strains has been created for the production of DNA vectors included in the composition of the DNA vaccine on a commercial scale.
Patent for base vector GDTT1.8NAS12 No 2712838 was issued on 31.01.2020 (priority date 04.09.2018).
The intellectual property of the SARS-CoV-2 DNA vaccine is protected. A package of international patent procedures was initiated, priority date - 20 April, 2020.
Initial in vitro studies, confirming the DNA vaccine effectiveness, have been performed.
Technological documentation for industrial production, ensuring acceptable price parameters, has been prepared.
preparation for the launch of preclinical studies on rats to assess a specific pharmacological activity of the DNA vaccine is under way.
preparation for the launch of preclinical studies to assess the acute and chronical toxicity is under way.
The task of the project is a construction, study and launch onto the market of a DNA vaccine for SARS-CoV-2 virus as a composition of gene therapy DNA vectors based on gene therapy DNA vector GDTT1.8NAS12, combining the following properties:
I. Efficiency of gene therapy and vaccine DNA vectors in order to increase the expression level of target gene in eukaryotic cells included in the DNA vaccine and the DNA vaccine.
II. Possibility of safe use in human gene therapy and vaccination due to the absence of regulatory elements representing the nucleotide sequences of viral genomes in the gene therapy DNA vectors.
III. Possibility of safe use in human gene therapy and vaccination due to the absence of antibiotic resistance genes in the gene therapy DNA vector.
IV. Producibility and constructability DNA vaccine on an industrial scale.
The effectiveness of DNA vaccine under point I is ensured by including in its composition the optimal number of gene therapy DNA vectors based on the gene therapy DNA vector GDTT1.8NAS12 carrying sequences that encode the most immunogenic epitopes of SARS-CoV-2 proteins. This approach is desirable due to the fact that when constructing a single gene therapy DNA vector to which several sequences encoding immunogenic epitopes of SARS-CoV-2 proteins have been cloned, the expression level of therapeutic genes encoding viral antigens can be reduced due to an increase of the gene therapy vector length, which reduces the efficiency of DNA vector penetration into the cells.
Points II and III are provided for herein in line with the recommendations of the state regulators for gene therapy medicines and, specifically, the requirement of the European Medicines Agency to refrain from adding antibiotic resistance marker genes to newly engineered plasmid vectors for gene therapy (Reflection paper on design modifications of gene therapy medicinal products during development / 14 December 2011 EMA/CAT/GTWP/44236 /2009 Committee for advanced therapies) and refrain from adding viral genomes to newly engineered plasmid vectors for gene therapy (Guideline on the quality, non-clinical and clinical aspects of gene therapy medicinal products / 23 March 2015, EMA/CAT/80183/2014, Committee for Advanced Therapies).
The last task of the project is a construction of strains carrying gene therapy DNA vectors for the development and production of these gene therapy DNA vectors and DNA vaccines on an industrial scale.
For more information, see our presentation: download here