Targeting the variable surface of African trypanosomes with variant surface glycoprotein-specific, serum-stable RNA aptamers.
African trypanosomes cause sleeping sickness in humans and Nagana in cattle. The parasites multiply in the blood and escape the immune response of the infected host by antigenic variation. Antigenic variation is characterized by a periodic change of the parasite protein surface, which consists of a variant glycoprotein known as variant surface glycoprotein (VSG). Using a SELEX (systematic evolution of ligands by exponential enrichment) approach, we report the selection of small, serum-stable RNAs, so-called aptamers, that bind to VSGs with subnanomolar affinity. The RNAs are able to recognize different VSG variants and bind to the surface of live trypanosomes. Aptamers tethered to an antigenic side group are capable of directing antibodies to the surface of the parasite in vitro. In this manner, the RNAs might provide a new strategy for a therapeutic intervention to fight sleeping sickness.
Lorger
Mihaela
M
Department of Microbiology and Genetics, Darmstadt University of Technology, 64287 Darmstadt, Germany.
Engstler
Markus
M
Homann
Matthias
M
Göringer
H Ulrich
HU
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D000940:Antigenic Variation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D015195:Drug Design; D005818:Genetic Engineering / Q000379:methods; D008024:Ligands; D008968:Molecular Conformation; D015394:Molecular Structure; D012313:RNA / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000187:drug effects / Q000235:genetics / Q000276:immunology*
D000906:Antibodies; D008024:Ligands; D014643:Variant Surface Glycoproteins, Trypanosoma; D012313:RNA