Potential of RH5 Antisense on Plasmodium falciparum Proliferation Abatement

Infections by , 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 regio...

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Published inIranian journal of parasitology Vol. 17; no. 4; pp. 525 - 534
Main Authors Razavi Vakhshourpour, Sepand, Nateghpour, Mehdi, Shahrokhi, Nader, Motevalli Haghi, Afsaneh, Mohebali, Mehdi, Hanifian, Haleh
Format Journal Article
LanguageEnglish
Published Iran Tehran University of Medical Sciences 01.10.2022
Subjects
Antisense
Blood
Cell division
Gene expression
Genomes
Laboratories
Ligands
Malaria
Original
Parasites
Parasitology
Plasmodium falciparum
Proteins
Malaria
Plasmodium falciparum
Antisense
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Summary:Infections by , 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 gene. 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. genes start codon regions selected as conserved region besed on alignment results. Gap- -As which was complementary to sequence surrounding AUG start codon significantly reduced parasite growth (>90% at 50 nM) compared to sense sequence control (Gap- -Se) (17%), ( <0.001). transcripts were dramatically reduced after exposed to ODNs at a concentration of 5-500 nM for 48 h. 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.
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ISSN:1735-7020
2008-238X
DOI:10.18502/ijpa.v17i4.11280