The Institute of Biophysics and Cell Engineering offers consumers a method (technology) for the genetic modification of dermal fibroblasts using CRISPR/CAS9 target nuclease technology under a commercial agreement with technical assistance and/or a license agreement and is looking for partners to conclude a technical cooperation agreement.

Genetic modification of dermal fibroblasts using targeted (programmable) nuclease technology represents one of the most promising areas in modern regenerative medicine and medical biotechnology.

Importance and relevance.
1. Therapy for severe hereditary skin diseases.
For many genetic dermatoses, conventional medicine offers only symptomatic treatment. Targeted nucleases make it possible to address the root cause of the pathology:
• Epidermolysis bullosa (“butterfly children”): Modifying fibroblasts allows for the correction of mutations in genes encoding collagen (e.g., "COL7A1") or laminin. Reintroducing these corrected cells (autologous transplantation) restores skin structural integrity.
• Ehlers-Danlos syndrome and other collagenopathies: Precise editing of defective genes helps restore proper biosynthesis and the architecture of the extracellular matrix.

2. Combating skin aging and aesthetic medicine.
Fibroblasts are the first cells to undergo chrono- and photo-aging, losing their ability to produce collagen and hyaluronic acid.
• Rejuvenating the cellular pool: CRISPR technology can be used to activate “dormant” youth-associated genes or suppress genes responsible for cellular aging (senescence).
• Reducing oxidative stress: Modifying pathways that regulate defense against free radicals enables the creation of fibroblasts with enhanced resistance to ultraviolet (UV) radiation and toxins.

3. Treatment of chronic wounds, scars, and burns. Impaired fibroblast function leads to pathological tissue healing.
• Diabetes mellitus and trophic ulcers: Local administration of fibroblasts with enhanced expression of growth factors (such as VEGF or PDGF) stimulates angiogenesis and accelerates wound closure.
• Prevention of keloid scars: Targeted silencing of genes responsible for the excessive synthesis of fibrous tissue (e.g., components of the TGF-beta signaling pathway) prevents the formation of disfiguring scars.

4. An ideal cellular model: Safety and accessibility.
Dermal fibroblasts are an almost perfect subject for cellular engineering:
• Ease of acquisition: A skin biopsy is a minimally invasive, safe, and painless procedure.
• High proliferative potential: These cells multiply readily in a laboratory setting (in vitro), providing sufficient material for genetic editing and subsequent screening.
• A platform for reprogramming: Modified fibroblasts can easily be converted into induced pluripotent stem cells (iPSCs) for the regeneration of various other organs.

Using CRISPR/Cas9 targeted nuclease technology, the Institute of Biophysics and Cell Engineering has developed a method for the genetic modification of dermal fibroblasts carrying a mutation in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR) protein—the mutation responsible for cystic fibrosis.

A protocol has been developed for the genetic modification of mesenchymal stem cells and skin fibroblasts using CRISPR/Cas9 technology, aimed at correcting mutations or introducing changes to the nucleotide sequence that encodes a specific gene.

CRISPR/Cas9 technology holds promise for creating cellular test systems for hard-to-treat human genetic diseases; for developing drug candidates and treatment protocols; for generating a range of new biomedical products for regenerative medicine; and for establishing protocols for genome editing in cells derived from patients with hereditary diseases.

This information is featured in the Catalog "100 Best Developments of the National Academy of Sciences of Belarus for the National Economy (2022–2023)" 2024, pp. 214–215 and the Catalog "Advanced Developments of the National Academy of Sciences of Belarus," 2024, pp. 224–225. (in Russian)

Dermal fibroblasts play a key role in maintaining skin structure, synthesizing the extracellular matrix (collagen, elastin), and facilitating wound healing. The use of systems such as CRISPR/Cas9, TALEN, or ZFN (zinc-finger nucleases) for precise editing of these cells opens up revolutionary possibilities.

CRISPR/Cas9 technology holds great promise for creating cellular test systems for intractable human genetic diseases, developing drug candidates and associated treatment protocols, generating a range of novel biomedical products for regenerative medicine, and establishing protocols for genome editing in patients with hereditary disorders.

There are no domestic or foreign analogues.

A laboratory protocol has been developed.

The Institute of Biophysics and Cell Engineering has completed research on "The study of signaling processes
in animal and plant cells and the molecular mechanisms of their functioning." The results were used in the development of the methodology.

The Institute of Biophysics and Cell Engineering is a leading scientific institution in the Republic of Belarus, specializing in genetic engineering, immunology and allergology, nanotheranostics and personalized nanomedicine, as well as experimental and applied virology.

The Institute’s fundamental and applied research areas include:

In the field of medical biotechnologies:
- Genetic engineering: development of innovative biomedical cell products based on genetically modified cells.
- Immunology and allergology: development of new methods for the diagnosis and treatment of allergic diseases and immune dysfunctions.
- Innovative vaccines: development of prototypes for domestic DNA and RNA vaccines for the prevention of viral diseases.
- New diagnostic approaches: development of novel technologies for the early diagnosis of diseases and methods for personalized medicine aimed at improving human quality of life.
- Genome editing: editing of somatic and induced pluripotent stem cells, enabling the treatment of various diseases, including rare (orphan) and genetic disorders.
- Synthetic morphogenesis: including the engineering of tissues and organs.

In the field of bioinformatic technologies:
- Structure-based design of next-generation drugs, including the development of innovative targeted anti-tumor and antiviral agents using structural bioinformatics methods.
- Synthesis of targeted therapeutic agents and their *in vitro* testing.

In the field of nanotheranostics and personalized nanomedicine:
- Development of targeted delivery systems for next-generation therapeutic agents using nanomaterials.
- Development of biological biochips for disease diagnosis. - Research into a wide range of biocompatible nanomaterials for the development of biomedical cell products, artificial organs, and novel materials with antimicrobial, antiviral, and anti-inflammatory properties.

Activities of the Center for Experimental and Applied Virology:
- Cultivation of viruses and the development of new methods for culturing human viruses to create tools for the diagnosis, medical prevention, and treatment of viral diseases.
- Development of vaccine prototypes, including those for influenza (inactivated and recombinant), African swine fever (vector-based), and pulmonary tuberculosis (a therapeutic vaccine based on donor dendritic cells), as well as innovative anti-influenza agents.

In recent years, the Institute has carried out a number of international contracts and agreements within the framework of European Union programs, as well as in collaboration with leading scientific centers, foundations, and organizations.

Official website of the Institute of Biophysics and Cell Engineering.

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