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Our Focus Areas

Our developments:

We have developed innovative gene therapy DNA vectors series "VTvaf17" and "GDTT1.8NAS". Key differences of these  DNA-vectors from the existing plasmid vectors:

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  1. Safe to use due to absence of antibiotic resistance genes and sequences of viral genomes in the vector

  2. Minimal size of the vector ensuring efficient delivery of therapeutic genes

  3. Manufacturability (up to 200 mg of DNA from 1 litre of the bacterial culture)

           "Genetic Diagnostics and Therapy 21" Ltd. together with a group of partner companies and scientists from Russia, GB, Sweden, etc specializing in genetic engineering and biotechnology are implementing a comprehensive project to create, research and bring to market gene therapy non-viral DNA vectors based on the "VTvaf17" and "GDTT1.8NAS" series for the treatment of several diseases (over 15 nosologies, about 90 specialized DNA vectors) and their use in the manufacture of personalized biomedical cellular products.

           There are currently a number of limitations to the use of DNA vectors as gene therapy agents: a) the presence of antibiotic resistance genes within vectors, b) the risk of recombination for constructs designed for transient expression only, c) the presence of viral regulatory sites that enhance expression. For example, the European Medicines Agency considers it necessary to avoid introducing markers of antibiotic resistance into DNA vectors under development 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)]. The presence of regulatory elements represented by viral genome sequences is also undesirable [Guideline  on the quality, non-clinical and clinical aspects  of gene therapy medicinal products, 23 March 2015  EMA/CAT/80183/2014)], FDA Guidance for Industry: Environmental Assessment of Human Drug and Biologics Applications, July 1998- Draft Guidance for Industry: Determining the Need for and Content of Environmental Assessments for Gene Therapies, Vectored Vaccines, and Related Recombinant Viral or Microbial Products FDA-2014-D-0663].

           "Platform" DNA vector solutions of these series were created taking into account these regulatory limitations and are characterized by common strategic approaches: the absence of antibiotic resistance genes in the DNA vectors, which eliminates the possibility of antibiotic-resistant strains of microorganisms; the vectors also do not contain regulatory sequences from viral genomes, which reduces the risk of spontaneous induction of onco-transformation to almost zero.

           However, the DNA vectors of these series differ in terms of structure, size, tissue specificity, scope of application ("platform solution", therapeutic vector or vector for genome editing of animal/human/plant cells).

A distinctive, unparalleled feature of these DNA vectors is that the strains for their production provide an opportunity for positive selection that does not involve the use of antibiotics. In addition to safety, this approach also ensures a very high product yield (up to 200 mg/litre of bacterial culture).

           The safety and functionality of the concept of the developed DNA vectors is further confirmed by the fact that gene therapy product GENOTEROSIL (for activation of osteogenesis in difficult to heal fractures) comprising 4 therapeutic DNA vectors has proven effective and safe in preclinical and clinical phase I studies and is currently in phase II-III clinical trials.

Currently, we have the following DNA vectors in our arsenal:

Universal DNA platform vectors

  1. VTvaf17 DNA vector, contains the promoter region of the human elongation factor EF1A gene, vector size 3165 bp.

  2. GDTT1.8NAS12 DNA vector, contains the promoter region of the human elongation factor EF1A gene, vector size 2591 bp.

Tissue-specific DNA platform vectors

Tissue-specific DNA vectors are given in the table below:

DNA platform vectors for genome editing

  1. VTvaf17-Cas9 DNA vector for heterologous expression of this target gene in human and animal cells by various methods of genomic editing, contains promoter region of EF1A human elongation factor gene and Cas9 target gene, vector size 7351 bp.

  2. VTvaf17-Act1-Cas9 DNA vector for heterologous expression of this target gene in plant cells by various genomic editing techniques, contains Act1 promoter-regulator site (promoter region of rice actin gene), vector size 7369 bp.

Gene therapy DNA vectors

DNA vectors for increasing the expression level of a target gene in humans and animals), including by introducing human or animal cells into human or animal organs and tissues. There are 87 gene therapy DNA vectors in the collection; all positions contain the promoter region of the human elongation factor EF1A gene (the list is given in the table):

On the basis of various combinations of the given DNA vectors, gene therapy drugs were formed in 16 therapeutic directions: Female idiopathic infertility, Activation of osteogenesis in hard-healing fractures, Minimization of scars in surgery and traumatology, Mucoviscidosis / Cystic fibrosis, Erectile dysfunction, Alopecia, Neovascularity, Epidermolysis bullosa, Parodontosis, Therapeutic immunomodulation, Spondylosyndesis, Oxidative stress, Neoinnervation, Age-specific changes of skin, Therapeutic immunomodulation, Neurodegenerative diseases, Hemochromatosis.

DNA vectors for transfection of immunocompetent cells

           (CAR-T, CAR-NK, CAR-DC and others) as part of adoptive cell therapy (ACT) for oncological patients. The company is currently working on a project "Development of a range of non-viral genetically engineered tools for the expression of chimeric antigen receptors for transfection of immunocompetent cells for personalised cellular oncotherapy".  The project concept is as follows: not a single molecular genetic construct for oncotherapy with transfected immunocompetent cells is created, but a line of specialised 4th to 5th generation DNA vectors for transfection of these cells (T-lymphocytes, NK cells, Dendritic cells) within oncotherapy procedures targeting both different oncological nosologies (including solid tumours) and taking into account the neoantigenic determinants and immunophenotype of patients. Digital data obtained from the preliminary study of the patient and his/her tumour material will provide an operational opportunity to select from a range of GMP-compliant and ready-to-use genetically engineered constructs - one or more items best suited to that particular patient, i.e. carrying the optimal onco-targets, costimulatory/suppressive domains for CAR therapy of that patient. Currently, it has been determined that the range will include several non-viral genetically engineered transfection tools. This project is due to be completed in 2024.

           Developers have performed extensive patent protection of intellectual property of platform and therapeutic solutions in the form of patents for inventions, including depositing producer strains in international depositories (All-Russian Collection of Industrial Microorganisms VKPM and National Collections of Industrial, Food and Marine Bacteria NCIMB).

 

 

The unique qualities of the "VTvaf17" and "GDTT1.8NAS" series DNA vectors. DNA vectors combine efficiency, safety, compliance with stringent regulatory requirements, manufacturability providing affordable pricing and a wide range of patent protection.

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