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

Published

Journal Article

There are many protein and DNA based therapeutics under development in the biotechnology and pharmaceutical industries. Key delivery challenges remain before many of these biomolecular therapeutics reach the clinic. Two important barriers are the effective targeting of drugs to specific tissues and cells and the subsequent intracellular delivery to appropriate cellular compartments. 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 offer improved performance in pre-targeting delivery strategies. In addition, we review recent work with pH-responsive polymers that mimic the membrane disruptive properties of viruses and toxins. These polymers could serve as alternatives to fusogenic peptides in gene therapy formulations and to enhance the intracellular delivery of protein therapeutics that function in the cytoplasm.

Full Text

Duke Authors

Cited Authors

  • Stayton, PS; Hoffman, AS; Murthy, N; Lackey, C; Cheung, C; Tan, P; Klumb, LA; Chilkoti, A; Wilbur, FS; Press, OW

Published Date

  • March 2000

Published In

Volume / Issue

  • 65 / 1-2

Start / End Page

  • 203 - 220

PubMed ID

  • 10699281

Pubmed Central ID

  • 10699281

Electronic International Standard Serial Number (EISSN)

  • 1873-4995

International Standard Serial Number (ISSN)

  • 0168-3659

Digital Object Identifier (DOI)

  • 10.1016/s0168-3659(99)00236-9

Language

  • eng