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Preliminary In Silico Study of a Novel Paratransenic Weapon Against Malaria: Modifying Wild Plasmodium Populations via Recombinant Mosquito Symbiont
Malaria is an infectious illness caused by Plasmodium parasites and vectored by Anopheles
mosquitoes. Recent developments in genetic engineering have opened the doors to paratransgenesis
as a technique to combat malaria. This preliminary in silico project aims to investigate an unorthodox
paratransgenic approach to eliminating Plasmodium cells in the mosquito. A recombinant Ti plasmid,
intended to be hosted in the mosquito gut bacteria, Asaia bogorensis, was designed to confer two
abilities: detect Plasmodium protein biomarkers via the FecA biosensor and, upon detection,
selectively transfer a toxin gene to kill only Plasmodium cells. However, this FecA biosensor was
untested. To test the feasibility of this design, 15 Plasmodium proteins highly expressed throughout
the parasite’s sporogenic cycle underwent molecular docking with FecA. The binding affinities were
analyzed and checked with t-tests to ascertain statistical significance. Four had shown strong binding
with FecA: GGCS, PPM5, LAP1/CCp3/SR, and IMC1a. Eight proteins were statistically insignificant but
still viable biomarker candidates: FabB/F, P28, SHLP1, CelTOS, c-CAP, CSP, P25, and GST. Three proteins
were incompatible with FecA: MAOP, SOAP, and CTR. Although these results were promising, in vivo
experiments are still required to confirm whether these proteins could properly trigger the gene
transfer function. Future studies could investigate the twelve proteins with potential elucidated in this
project.
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