Serum-stable RNA aptamers to an invariant surface domain of live African trypanosomes.
African trypanosomes are extracellular blood parasites that cause sleeping sickness in humans and Nagana in cattle. The therapeutics used to control and treat these diseases are very ineffective and thus, the development of new drugs is urgently needed. We have previously suggested to use trypanosome-specific RNA aptamers as tools for the development of novel trypanocidal compounds. Here, we report the selection of a 2'-NH(2)-modified RNA aptamer that binds to live trypanosomes with an affinity of 70 +/- 15 nM. The aptamer adopts a stable G-quartet structure and has a half-life in human serum of > 30 h. RNA binding is restricted to the flagellar attachment zone, located between the cell body and the flagellum of the parasite. We demonstrate that antigen-tagged preparations of the aptamer can bind to live trypanosomes and that they can be used to re-direct immunoglobulins to the parasite surface.
Homann
Matthias
M
Institute of Microbiology and Genetics, Darmstadt University of Technology, Schnittspahnstrasse 10, D-64287 Darmstadt, Germany. goringer@hrzpub.tu-darmstadt.de
Lorger
Mihaela
M
Engstler
Markus
M
Zacharias
Martin
M
Göringer
H Ulrich
HU
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D004591:Electrophoresis, Polyacrylamide Gel; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000276:immunology / Q000494:pharmacology*; D014353:Trypanosomiasis, African / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000187:drug effects* / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D052157:Aptamers, Nucleotide; D014344:Trypanocidal Agents; D014643:Variant Surface Glycoproteins, Trypanosoma; D012313:RNA