ABSTRACT
INTRODUCTION A central paradigm of the biopharmaceutical industry is to identify a natural protein having a desired biochemical activity and then use recombinant methods to produce that protein in sufficient quantities for biological testing and ultimately, for therapeutic use, usually as an injected drug. For proteins intended for use as human pharmaceuticals, a key experiment will be to test the protein for efficacy in an animal model of the human disease. Testing of these proteins, however, may be limited by factors other than their intrinsic biochemical activity. Poor solubility, stability, and pharmacokinetic half-life are common issues hampering preclinical and clinical testing of protein pharmaceuticals. In particular, low-molecular-weight proteins usually show rapid clearance in vivo, making it difficult to deliver a high-enough dose to achieve the desired biological effect. Although smaller molecular size may have advantages, for example, in penetration into solid tumors, for many injected therapeutics, prolonged half-life and infrequent dosing are often preferred.
