Gene Technology in Drug Research

The key to modern drug discovery is gene technology. It enables the production of pure proteins, targeted mutagenesis to elucidate functional and mechanistic properties, the development of animal models by knocking in and out specific genes, the activation or silencing of genes, and individual somatic gene therapy. Elucidation of the genetic code, recombinant production of genes and gene products, and the polymerase chain reaction have been essential technologies. The sequencing of the human genome has revealed the composition of our genes and provided many functional insights. It contains about 25,000 genes, of which about 21,500 are translated into proteins and some sequences are non-coding RNAs. About 95% of the genome contains numerous sequences and signals that control the regulation of the genome. Functional classification of gene products has been achieved for a significant portion of the genome. To study the relevance of blocking the function of a gene product in a disease situation, genes can be knocked in and out and tested in animal models. Turning genes on and off is of paramount importance in drug discovery because it provides critical information about the relevance of a putative therapeutic intervention. In vitro models for drug screening could only be developed once proteins could be produced in pure form and in high yield. Genes can be silenced by RNA interference. This eliminates mRNAs with specific sequences. This principle can also be used for therapy. Chemical modifications of RNA molecules are aimed at improving their transport properties, immunogenicity and stability. The PROTAC approach, which stands for Proteolysis Targeting Chimera, can be used to cause the selective proteolytic degradation of pathogenic proteins into amino acids by the cell’s own protein degradation machinery. The proteome reflects the totality of all proteins in a cell at a given time and under well-defined conditions. Its composition changes dynamically and differs between healthy and diseased states or under the influence of therapeutic treatments. Differences in expression patterns indicate the involvement of proteins in a disease situation. Biomolecules can be immobilized on microarray chips. In particular, RNA, DNA and their oligonucleotides are anchored on these chips to extract complementary RNA or DNA sequences from large mixtures. By appropriate fluorescence labeling, target sequences can be “fished” and expression patterns of cells can be studied. Polymorphisms, particularly single nucleotide polymorphisms (SNPs), are variations in the composition of the genome of a species. These changes make individuals different, and some SNPs confer susceptibility or resistance to disease or influence cellular response to a drug. Differences in individual genomes may be the key to individualized and personalized drug therapy. Genetic differences may also underlie the development of a disease. Epigenetics regulates the transcription process not by changing the genetic sequence of DNA, but by regulating how genes are read from DNA. Lifestyle, experience and environment affect genes through the epigenome. Gene therapy attempts to replace a defective or missing gene in a patient’s cells. This would eliminate the genetic disease for the individual. Retroviruses are used and a nucleic acid segment encoding the protein to be replaced is introduced into the patient’s genome. The retroviruses transcribe this information into DNA and integrate it into the DNA of the patient’s cells. The CRISPR-Cas9 method is a highly precise genetic scissors that may make it possible to easily replace diseased genes with healthy ones. https://sn.pub/54f7da