Strategies for the design of drug therapies containing engineered proteins

Drug therapies based on engineered proteins introduced new paradigms in the treatment of diseases in the late 20th and early 21st centuries. Today, engineered proteins are among the best-selling pharmaceuticals worldwide and are proving to be competitors, and in some cases significantly superior, to the drugs based on small chemical molecules. In the article, using documentary methods for analyzing published scientific data from preclinical and clinical trials of engineered proteins for therapeutic purposes, modern designs of therapeutic engineered proteins are considered in terms of increased affinity, specificity, stability, cell permeability and pharmacokinetics, as well as reduced doses in connection with possible unwanted immunogenicity. Different strategies for the design of engineered proteins, representing various structural modifications, are considered: 1. Site-specific mutagenesis; 2. Antibody–drug conjugates; 3. PEGylation; 4. Glycosylation; 5. Fc synthesis; 6. Synthesis of other proteins; 7. Lipidation; 8. Attachment of non-PEG polymers; 9. Supercharging; 10. Computational design.