Iranian journal of basic medical sciences · 2025
Recent advances in the genetic engineering of the Leishmania parasite and anti-cancer properties.
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Rahim Saeid, Yousofi Darani Hossein, Khanahmad Hossein, Pourmoshir Nadia, Bakhshiyani Zahra, Saberi Sedigheh
Аннотация
Leishmaniasis is a tropical disease caused by Leishmania species, affecting millions of people worldwide and contributing to substantial morbidity and mortality. Advances in genetic engineering technologies, particularly CRISPR/Cas9, plasmid shuffling, and DiCre-based systems, have significantly enhanced our understanding of Leishmania biology. These approaches have enabled precise gene editing, functional analysis of essential genes, and the development of genetically attenuated strains with potential applications in vaccine design and drug discovery. Gene editing tools have also allowed the identification of key virulence factors and pathways involved in parasite survival and modulation of the host immune system. These insights have opened new directions for therapeutic strategies against leishmaniasis. Interestingly, recent findings highlight notable similarities between leishmaniasis and cancer, including immune checkpoint involvement, chronic inflammation, and shared molecular targets. Leishmania's ability to influence host immune responses and epigenetic mechanisms mirrors certain cancer-related processes. Moreover, compounds originally developed for cancer treatment, such as miltefosine and topoisomerase inhibitors, have shown effectiveness against Leishmania, supporting the potential for cross-applications. This review outlines recent developments in Leishmania genetic engineering and explores how these advancements can contribute to both anti-leishmanial and anti-cancer therapies. By emphasizing overlapping biological pathways and therapeutic targets, this work suggests innovative approaches to address two major global health challenges.