In general, therapeutic proteins can be highly specific for malignant cells and show only mild toxic side effects. However, the half-lives of these molecules in vivo are short; therefore, they are not ideal drug candidates. Improving the pharmacokinetic properties of proteins used for therapeutic purposes is crucial to developing stable protein-based drugs. Modern protein engineering techniques can enable the efficient development of long-acting protein therapies with high biological activity, increased bioavailability, and reduced immunogenicity.

PEGylation and protein fusion technologies are two of the main engineering tools used to develop long-acting proteins. The former involves conjugating proteins to polyethylene glycol, while the latter involves the fusion of an immunoglobulin Fc fragment or albumin to a target protein. Both methods increase the in vivo half-life of a protein. Examples of such drugs include Peg-Intron, Neulasta, Mircera, Cimza, Levemir and Victoza (diabetes drugs), and Enbrel and Orencia (rheumatoid arthritis drugs). Other novel technologies, such as PASylation (which fuses polypeptides to proteins), XTEN technology, and methods involving the use of small antibody fragments are also being developed.