potential of rh5 antisense on plasmodium falciparum proliferation abatement

Background: infections by plasmodium falciparum, are becoming increasingly difficult to treat. therefore, there is an urgent need for novel antimalarial agents’ discovery against infection. in present study, we described a 2’-o-methyl gapmer phosphorothioate oligonucleotide antisense targeting translation initiation region of 3d7 strain rh5 gene.methods: the study was conducted in pasteur institute of iran in 2020. odns effects were measured by microscopic examination and real time rt-pcr. for microscopy, microplates were charged with 2’-ome odns at different dilutions. unsynchronized parasites were added to a total of 0.4 ml (0.4% parasitemia, 5% red blood cells), and slides were prepared. proportion of infected cells was measured by counting at least 500 red blood cells.results: rh5 genes start codon regions selected as conserved region besed on alignment results. gap-rh5-as which was complementary to sequence surrounding aug rh5 start codon significantly reduced parasite growth (>90% at 50 nm) compared to sense sequence control (gap-rh5-se) (17%), (p<0.001). rh5 transcripts were dramatically reduced after exposed to odns at a concentration of 5-500 nm for 48 h.conclusion: gemnosis delivery of a chimeric gapmer ps-odn with 2’-ome modifications at both sides had high antisense activity at low concentrations (10-100 nm) and shown a good efficiency to reach to target mrna in human rbcs. anti-parasite effect was correlated to reduction of target gene mrna level. in addition, 2’-ome odns free delivery is an effective way and does not need any carrier molecules or particles.