Novel approaches for HTLV-1 therapy: innovative applications of CRISPR-Cas9

Author(s)

Domingues, Wilson ; Folgosi, Victor angelo ; Sanabani, Sabri Saeed ; Leite Junior, Pedro Domingos ; Assone, Tatiane ; Casseb, Jorge

• Document type: Journal article
• Source: Revista do Instituto de Medicina Tropical de São Paulo; v. 66, p. 9-pg., 2024-01-01.

Abstract

The human T-cell lymphotropic virus type 1 (HTLV-1) is a single-stranded positive-sense RNA virus that belongs to the Retroviridae family, genus Deltaretro, and infects approximately five to 10 million people worldwide. Although a significant number of individuals living with HTLV-1 remain asymptomatic throughout their lives, some develop one or more severe clinical conditions, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a progressive and debilitating disease, and/or a subtype of non-Hodgkin's lymphoma with a more threatening course known as adult T-cell leukemia/lymphoma (ATLL). Moreover, current therapeutic options are limited and focus primarily on treating symptoms and controlling viral latency. CRISPR-Cas9 gene editing is proposed as a promising tool to address the intricate links associated with HTLV-1. By targeting or silencing key genes during initial infection and dysregulating immune signaling pathways, CRISPR-Cas9 offers potential intervention opportunities. In this review, we address the therapeutic potential of CRISPR-Cas9 gene editing, as well as examine the primary mechanisms involved in editing potential target genes and discuss the existing evidence in the current scientific literature. (AU)

• FAPESP's process: 18/07239-2 - Incidence, risk factors, and pathogenic mechanism of neurocognitive disorders (HAND) among HIV-1-infected subjects
• Grantee: Jorge Simao do Rosario Casseb
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 22/00132-3 - Incidence, risk factors, and pathogenic mechanisms in HIV-1-associated neurocognitive disorders (HAND)
• Grantee: Wilson Domingues
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 23/14320-9 - Treatment strategies for HTLV-1 infection: gene editing and immune modulation in non-human primate cells
• Grantee: Víctor Ângelo Folgosi
• Support Opportunities: Scholarships in Brazil - Doctorate