Investigating the impact of HIS-1 and HSP-70 genes on drug response and pathology of Leishmania major using antisense oligonucleotides

Leishmaniasis is a protozoan disease caused by the protozoan Leishmania spp. and presents a wide spectrum of manifestations. Researchers are currently unable to control and treat the different forms of leishmaniasis, and effective vaccines and treatments are not yet available. This study aimed to assess the pathological aspects and drug susceptibility of L. major treated with antisense oligonucleotides (ASO) targeting the HSP-70 and HIS-1 genes. This study investigates the anti-leishmanial properties of antisense oligonucleotides (ASO) directed against the HSP-70 and HIS-1 genes, which play critical roles in stage differentiation and resistance to anti-leishmanial drugs. The experiments were conducted using L. major promastigotes and amastigotes in vitro and a mouse model for cutaneous leishmaniasis (CL). Our results indicated that the expression of the HSP-70 and HIS-1 genes was significantly reduced in the group receiving antisense oligonucleotides (ASO). In the group treated with HSP-70 ASO, the amastigote count in macrophages was significantly reduced compared to the other groups. The findings from the in vivo experiments revealed that in the group receiving HIS-1 ASO, the size of the CL lesion was significantly reduced, and susceptibility to glucantime was significantly increased compared to the other groups. The results of the current study demonstrated that HIS-1 and HSP-70 ASOs successfully inhibit the pathogenicity of the L. major and decrease the lesion size of CL. ASO as a novel technique in genetic manipulation also revealed that it can aid in the control and prevention of various diseases.