Molecular engineering of proteins and polymers for targeting and intracellular delivery of therapeutics

There are many protein acid DNA based therapeutics under development in the biotechnology and pharmaceutical industries. Key delivery challenges remai n before many of these biomolecular therapeutics reach the clinic. Tno impo rtant barriers are the effective targeting of drugs to specific tissues and cells and the subsequent intracellular delivery to appropriate cellular co mpartments. In this review, we summarize protein engineering work aimed at improving the stability and refolding efficiency of antibody fragments used in targeting, and at constructing new streptavidin variants which may offe r improved performance in pre-targeting delivery strategies. In addition, w e review recent work with pH-responsive polymers that mimic the membrane di sruptive properties of viruses and toxins. These polymers could serve as al ternatives to fusogenic peptides in gene therapy formulations and to enhanc e the intracellular delivery of protein therapeutics that function in the c ytoplasm. (C) 2000 Elsevier Science BSI. All rights reserved.