利用RNA干扰技术双通道抑制弓形虫嘌呤补救合成途径的综述报告.docxVIP

利用RNA干扰技术双通道抑制弓形虫嘌呤补救合成途径的综述报告

Introduction

ToxoplasmosisisaworldwideparasiticinfectioncausedbytheprotozoanToxoplasmagondii.Thisparasitecaninfectvariousanimals,birds,andhumans.Inhumans,T.gondiiinfectioncancausesevereneurologicalandoculardiseases,particularlyinimmunocompromisedindividuals.Althoughfewdrugsareavailabletotreattoxoplasmosis,theirtoxicitiesandsideeffectslimittheirefficacy.Therefore,developingnewstrategiestocontrolT.gondiiinfectioniscrucial.RNAinterference(RNAi)isapowerfultooltostudygenefunctionandhasbeenusedtocontrolparasiticinfections.ThisreportaimstoreviewtheuseofRNAitotargetthepurinesalvagepathwayofT.gondii.

ThePurineSalvagePathwayofT.gondii

T.gondiiisanobligateintracellularparasitethatreliesonthehostcellspurinenucleotidesforitsownmetabolicprocesses.Thepurinesalvagepathwayisessentialforthesynthesisofpurinenucleotides,whicharerequiredforDNAandRNAsynthesis.ThesalvagepathwayofT.gondiioperatesinthecytosol,anditinvolvestheuptakeofpurinesfromthehostcellfollowedbytheirconversionintonucleotidesbyspecificenzymes.Thekeyenzymesofthepurinesalvagepathwayarehypoxanthine-guanine-xanthinephosphoribosyltransferase(HGXPRT)andadenosinephosphoribosyltransferase(APRT),whichcatalyzetheconversionofhypoxanthine/guanine/xanthineandadenosineintotheircorrespondingnucleotides.

RNAInterference

RNAiisagenesilencingmechanismthatoccursnaturallyincells.TheprocessinvolvesthecleavageofmRNAbysmallRNAmolecules,suchassmallinterferingRNAs(siRNAs)orshorthairpinRNAs(shRNAs),thatarecomplementarytothemRNA.RNAicanbeusedtoinhibitgeneexpressioninmanyorganisms,includingparasites,bydesigningsiRNAsorshRNAsthattargetspecificgenes.Onceinsidethecell,siRNAorshRNAbindstoacatalyticproteinknownasRNA-inducedsilencingcomplex(RISC).