Generation of species cross-reactive aptamers using "toggle" SELEX.

Published

Journal Article

Species cross-reactivity facilitates the preclinical evaluation of potentially therapeutic molecules in animal models. Here we describe an in vitro selection strategy in which RNA ligands (aptamers) that bind both human and porcine thrombin were selected by "toggling" the protein target between human and porcine thrombin during alternating rounds of selection. The "toggle" selection process yielded a family of aptamers, all of which bound both human and porcine thrombin with high affinity. Toggle-25, a characteristic member, inhibited two of thrombin's most important functions: plasma clot formation and platelet activation. If appropriate targets are available, the toggle strategy is a simple measure that promotes cross-reactivity and may be generalizable to related proteins of the same species as well as to other combinatorial library screening strategies. This strategy should facilitate the isolation of ligands with needed properties for gene therapy and other therapeutic and diagnostic applications.

Full Text

Duke Authors

Cited Authors

  • White, R; Rusconi, C; Scardino, E; Wolberg, A; Lawson, J; Hoffman, M; Sullenger, B

Published Date

  • December 2001

Published In

Volume / Issue

  • 4 / 6

Start / End Page

  • 567 - 573

PubMed ID

  • 11735341

Pubmed Central ID

  • 11735341

International Standard Serial Number (ISSN)

  • 1525-0016

Digital Object Identifier (DOI)

  • 10.1006/mthe.2001.0495

Language

  • eng

Conference Location

  • United States