Laboratory of Genetic Engineering

The laboratory was created in 1983.

Main areas of research

  • The study of the mechanisms of action of enzyme systems of nucleic acids matrix synthesis and gene expression regulation at the level of gene transcription. The work focuses on the study of the characteristics of the expression of thousands of genes by the method of transcription matrices and RT-PCR in various cardiological (hypertension, atherosclerosis) and oncological diseases (myxoma of the heart, melanoma).
  • Enzymology and protein engineering of fibrinolytic enzymes.

The most significant research results

Studies of the time-unequal reading of the matrix information of DNA and RNA polymerases led to the development of a large series of nucleotide analogs that terminate the growing chain of transcripts (replicas), one of which served as the basis for the development of an original antiretroviral drug, which, due to its low toxicity, is widely used to prevent AIDS in the newborn children. It was the first anti-AIDS tool developed in Russia and introduced into practice for the treatment of AIDS patients in the nineties of the last century.

In the study of gene expression in heart myxoma seven genes (PLA2G2a, MIA, PLTP, CFLB2, SPP1, TIMP1 and SLPI) were identified; their simultaneous high expression allows to uniquely diagnose myxoma, distinguishing it from others malignant heart tumors.

Melanoma is one of the most aggressive malignant neoplasms. Patients operated in time at the first or second stage of the disease are divided into three approximately equal in size groups: dying within 5 years after surgery, recurring within the same period and completely cured. Expression analysis of 12 genes: SILV, MLANA, TYR, WARS, BCL6, SPP1, TNC, FN1, NME1, CDKN2A (INK and ARF), TRPM1, DPP4 allowed us to develop a prognostic criterion with a specificity of 78% and a sensitivity of 100%, predicting a state of complete recovery.

In the study on the identification of genes that change their activity in peripheral blood lymphocytes in atherosclerosis and arterial hypertension and in the intimal cells of different types of atheromas during atherosclerosis, 13 genes were detected: CD14, CTSB, CD37, MSR1, PLTP, LIPA, CTSA, LCP1 , ACP5, CNSD, CD53, FPR3, SPI1. Their activities are highly correlated with the degree of atherosclerotic lesions in the intima. However, their activities in peripheral blood cells are highly correlated with hypertension and atherosclerosis. The activity of most of these genes is associated with monocytic cells. The activity of a part of these genes can be reduced, approaching the normal value by the treatment with calcium channel blockers.

Studies of the activity of genes associated with atherosclerosis in a heat wave model similar to the heat wave of the summer of 2010 in the European part of Russia were carried out. A completely reversible shift in the activity of these genes in healthy people in the direction of the values typical for patients with severe atherosclerosis has been shown.

One of the main achievements of the laboratory was the creation of a human urokinase analogue that unlike the natural enzyme, lacked the ability to activate the urokinase receptor, and creation on its basis of drugs Purolaza and Gemaza, widely used in cardiology and ophthalmology since 2000.

Research for the creation a direct-acting thrombolytic drug based on a modified human plasminogen gene are conducted. Unlike Purolaza, the plasminogen-based drug does not require the action of plasminogen activators and is itself an activator of a number of physiologically active enzymes, such as collagenase, for example. The preclinical studies of this drug have been completed.

Head of the laboratory – Dr. Robert Sh. BIBILASHVILI, PhD