Gene-Specific Antisense Oligonucleotide Therapy Targeting AMA1: A Potential Malaria Treatment.
- 1Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- 2Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran.
- 3Department of Biostatistics and Epidemiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Abstract
Background
We evaluated the effects of 2'-O-methyl (2'-OMe) antisense oligonucleotides targeting the apical membrane antigen 1 (AMA1) gene of Plasmodium berghei using In vivo and In vivo models.Methods
This study was conducted from 2019 to 2022 in Tehran, Iran. Anti-sense gapmer oligonucleotides targeting conserved regions of the AMA1 gene were designed using Vector NTI, mfold, and sfold and synthesized with 2'-OMe modifications. P. berghei ANKA cultures were treated with various ASO concentrations, and parasitemia was assessed by Giemsa-stained smears and real-time PCR. In vivo efficacy was evaluated in BALB/c mice infected intraperitoneally with P. berghei and treated subcutaneously with ASOs or control oligonucleotides; parasitemia was monitored microscopically.Results
Both antisense oligonucleotides showed low cytotoxicity, with cell viability exceeding 89% at the tested concentrations. In vitro, both antisense oligonucleotides significantly reduced parasitemia compared with the sense control (P=0.01), with no significant difference between the two antisense sequences (P>0.05). Both oligonucleotides also reduced AMA1 expression, with the 183-202 oligonucleotide showing the greatest inhibitory effect. In vivo, the AMA1 183-202-treated group showed significantly lower parasitemia on day 2 post-infection (P=0.048), while lower parasitemia was observed in the antisense-treated groups on subsequent assessment days.Conclusion
2'-O-methyl antisense oligonucleotides targeting AMA1 reduced parasite growth and AMA1 expression In vivo and were associated with reduced parasitemia in P. berghei-infected mice. These preliminary findings support further investigation of AMA1-directed antisense therapy as a potential gene-specific antimalarial strategy. Larger, adequately powered studies are required to confirm efficacy and evaluate ASO delivery, stability, safety, and durability of gene silencing.
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BibTeX
@article{hanifian2026genespecific,
title = {{Gene-Specific Antisense Oligonucleotide Therapy Targeting AMA1: A Potential Malaria Treatment.}},
author = {Haleh Hanifian and Nader Shahrokhi and Mehdi Nateghpour and Afsaneh Motevalli Haghi and Mehdi Mohebali and Abbas Rahimi Foroushani and Sepand Razavi Vakhshourpour},
journal = {Iranian journal of parasitology},
year = {2026},
month = jul,
doi = {10.18502/ijpa.v21i3.22593},
url = {https://europepmc.org/article/MED/42974492},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Gene-Specific Antisense Oligonucleotide Therapy Targeting AMA1: A Potential Malaria Treatment.
AU - Haleh Hanifian
AU - Nader Shahrokhi
AU - Mehdi Nateghpour
AU - Afsaneh Motevalli Haghi
AU - Mehdi Mohebali
AU - Abbas Rahimi Foroushani
AU - Sepand Razavi Vakhshourpour
PY - 2026
DA - 2026/07/01
JO - Iranian journal of parasitology
DO - 10.18502/ijpa.v21i3.22593
UR - https://europepmc.org/article/MED/42974492
AB - Background We evaluated the effects of 2'-O-methyl (2'-OMe) antisense oligonucleotides targeting the apical membrane antigen 1 (AMA1) gene of Plasmodium berghei using In vivo and In vivo models.Methods This study was conducted from 2019 to 2022 in Tehran, Iran. Anti-sense gapmer oligonucleotides targeting conserved regions of the AMA1 gene were designed using Vector NTI, mfold, and sfold and synthesized with 2'-OMe modifications. P. berghei ANKA cultures were treated with various ASO concentrations, and parasitemia was assessed by Giemsa-stained smears and real-time PCR. In vivo efficacy was evaluated in BALB/c mice infected intraperitoneally with P. berghei and treated subcutaneously with ASOs or control oligonucleotides; parasitemia was monitored microscopically.Results Both antisense oligonucleotides showed low cytotoxicity, with cell viability exceeding 89% at the tested concentrations. In vitro, both antisense oligonucleotides significantly reduced parasitemia compared with the sense control (P=0.01), with no significant difference between the two antisense sequences (P>0.05). Both oligonucleotides also reduced AMA1 expression, with the 183-202 oligonucleotide showing the greatest inhibitory effect. In vivo, the AMA1 183-202-treated group showed significantly lower parasitemia on day 2 post-infection (P=0.048), while lower parasitemia was observed in the antisense-treated groups on subsequent assessment days.Conclusion 2'-O-methyl antisense oligonucleotides targeting AMA1 reduced parasite growth and AMA1 expression In vivo and were associated with reduced parasitemia in P. berghei-infected mice. These preliminary findings support further investigation of AMA1-directed antisense therapy as a potential gene-specific antimalarial strategy. Larger, adequately powered studies are required to confirm efficacy and evaluate ASO delivery, stability, safety, and durability of gene silencing.
SN - 1735-7020
SN - 2008-238X
ER -