Development of new tools to control infections due to parasites of the Trypanosomatidae family
Keywords: Trypanosomiasis, Sleeping Sickness, Nanobody, Diagnostics, Drug-targeting
Antibody-based nanobody (Nb) technology has been developed at VIB, based on the discovery that natural heavy chain antibodies can be used for the engineering of very small nanometre-seized antibody fragments, that are characterized by: (i) their unique epitope recognition potential, (ii) their ease of production with recombinant expression as opposed to hybridoma production, (iii) the ease of selection by affinity panning, following in vivo affinity maturation, (iv) their improved stability when compared to conventional antibodies. In 2006, the accumulated Nb knowledge and technology culminated in the development of an experimental drug delivery method for trypanosomiasis (Baral et al. Nature Med. 2006 12(5):580-4). In addition, VIB also reported the use of nanobody tools for parasite detection in experimental trypanosomiasis in mice (Stijlemans et al. Biol Chem. 2004 279(2):1256-61). Building on these achievements, the project objectives of NANOTRYP are to (i) generate of a number of Nb libraries that are capable of recognizing all four major African trypanosome species, (ii) use these libraries for construction and testing of new trypanosomiasis diagnostic tools, and (iii) assess of the use of anti-trypanosome Nbs for drug targeting.
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Trypanosomiasis is a disease with a devastating socio-economic impact in Sub-Saharan Africa through the direct infection of humans and livestock. Even though diagnostic test and treatments exist, both suffer from serious drawbacks. While current diagnostics have limited specificity, current treatment schemes often results in severe negative side effects in patients, and even can be lethal. NANOTRYP will address to improvement of both diagnosis and treatment modalities for trypanosomiasis through Nanobody technology.
NATOTRYP aims at developing new simple to use Nanobody based diagnostic tests, reaching measurable outcomes such as (i) the development of a Nb-based diagnostic test for detection of parasites through antigen detection, both for HAT and animal trypanosomiasis, where a Nb-based dip-stick appears to be the most favourable tool, and (ii) the development of an Nb-based targeting strategy for site-specific drug delivery, in order to improve current anti-parasite therapies. In addition, NANOTRYP aims at an important involvement of the African science community both at the level of fundamental trypanosome research, as well as at the level of disease diagnostics, treatment and community awareness building.
Diagnosis and treatment of African trypanosomiasis