Inhibition of calreticulin by protein nanoparticles carrying antisense oligonucleotides reduce gene expression and infection of Trypanosoma cruzi trypomastigotes on mammalian cells.

BACKGROUND

Chagas disease, caused by the parasite Trypanosoma cruzi, is a neglected tropical disease that impacts millions of individuals. At least two drugs directed against the parasite (Benznidazole and Nifurtimox) have low effectiveness in treating Chronic Chagasic patients. The present work is focused on studying new strategies to develop innovative treatments.

METHODS

The strategy was based on the use of a virus-inspired protein (CBK12) that formed nanoparticles with antisense oligonucleotides (AON) against Calreticulin gene of T. cruzi. TcCRT has several functions in T. cruzi, such as participation in cell infection, modulation of the host's immune response, cell adhesion, control of the level of calcium, and in the folding of glycoproteins. T. cruzi trypomastigotes were incubated with the protein-CRT nanoparticle (CBK12+CRT), and several parameters were evaluated.

RESULTS

The results showed that CRT, Super Oxide Dismutase, and Glutathione Peroxidase presented gene expression reduction. Decreased parasite survival, altered parasite morphology, increased complement susceptibility, produced metabolic alteration, and substantially reduced mammal cell infection were also observed.

CONCLUSION

The results indicate that protein nanoparticles carrying antisense oligonucleotides are a promising strategy directed against T. cruzi.