Genetic engineering approaches to the development of modern therapeutics

Abstract

The classic approach to production of protein-based therapeutics is their isolation from natural sources. This approach was associated with a number of difficulties, such as collecting the primary material from natural sources, isolating and purifying the protein, and its standardizing. With the development of recombinant DNA technology, itbecame possible to obtain large quantities of protein preparations lacking any contaminations. Human insulin produced using recombinant DNA technology is the first commercial therapeutic obtained by this way. Due to the rapid development of genetic engineering technologies, a large number of proteins have been obtained inEscherichia colicells. In recent years, the approach for the development of drugs based on DNA molecules containing genes encoding therapeutic proteins has been developing more actively. Today, many scientists believe in the prospects of application of DNA vaccines. The ease of production, stability, the ability to mimic natural infections and elicit appropriate immune responses make this vaccine platform extremely attractive. Delivery and targeting of immunologically relevant cells are major tasks for maximizing the immunogenicity of DNA vaccines. Several different approaches that are currently being used to achieve this goal are discussed in this review. Pharmaceuticals based on nucleic acids have a number of undeniable advantages. The main options for prophylactic RNA vaccines, the methods used to deliver RNA to the cell, and methods for increasing the effectiveness of RNA vaccines are discussed. Usage of therapeutic drugs based on protein molecules and low molecular weight compounds is complicated by the fact that they cannot be targeted at a specific gene or its protein product, responsible for the occurrence of the disease. Action of nucleic acids can be directly directed to a particular DNA region in order to edit its nucleotide sequence. This method allows to correct a genetic defect, eliminating the cause of the disease. The principles of gene therapy and the successes achieved in this area are discussed. This review summarizes current achievements in the development of drugs based on recombinant proteins and nucleic acids.