Genetic Modulation Therapy Through Stem Cell Transplantation for Human Immunodeficiency Virus 1 Infection

Abstract

Highly active anti-retroviral treatment has changed the dimensions of the outcomes for patients suffering from human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). However, HIV infection is still an ailment which is spreading throughout the world extensively. Given the confinements of the present restorative methodologies and the non-availability of any strategic vaccination against HIV, there is a squeezing need to build a therapeutic treatment.Viral tropism for HIV includes CD4+ cells, macrophages, and microglial cells, and it is through binding with co-receptors C-C chemokine receptor type 5 (CCR5) and C-X-C chemokine receptor type 4 (CXCR4). While these cell types are present in all individuals, there are rare cases that stayed uninfected even after getting exposed to an overwhelming load of HIV. Research revealed a homozygous 32-base pair deletion (Δ32/Δ32) in CCR5. After careful consideration, a hypothesis was proposed a few years back that a cure for HIV disease is possible, through hematopoietic stem cells transplantation from a donor homozygous for the CCR5-Δ32 deletion.Hematopoietic stem cell (HSC) based quality treatment may serve as a promising tool as these perpetual, self-renewing progenitor cells could be modified to oppose HIV infection. If done properly, the changed HSCs would offer the permanent creation of genetically modified cells that are resistant to HIV infection and/or have improved hostility to viral action which will eventually clear the contaminated cells.The purpose of this review is to concentrate on two facets of HSC genetic treatment for potentially life-threatening HIV infection: building HIV-resistant cells and designing cells that can target HIV disease. These two strategic approaches can be the frontline of a quality treatment plan against HIV infection and, as an individual treatment or a combination thereof, has been proposed to possibly destroy HIV altogether.

Microglial Cells: The Main HIV-1 Reservoir in the Brain

“…From this example, the idea to build HIV-1 resistant cells has arisen (Barmania and Pepper, 2013). Clinical trials using ZFN targeting CCR5 are ongoing and deserve attention (Mehta et al, 2017). However, The CRISPR/Cas9 gene editing has become the tool of choice, since ZFN and TALEN are costly and time consuming.…”

“…This technology may serve to redesign the gene expression of cells such as CTLs so that they target more specifically HIV-1 infected cells. It is believed that by this way the antiviral immunity system could be more efficiently boosted against HIV-1 infected cells and activated reservoirs producing new virions (Mehta et al, 2017). We might even use a variation of the CRISPR/Cas9 technology to reactivate latently infected cells or to induce deep latency (Wang et al, 2018).…”

Hiv: O Uso Terapêutico De Células-Tronco Hematopoiéticas Sem Ccr5 Funcional

“…Os estudos evidenciaram que indivíduos com mutações no CCR5 podem fornecer proteção parcial ou total contra a infecção pelo HIV (MEHLOTRA, 2020) e, portanto, em pacientes com transplante de células-tronco hematopoiéticas sem CCR5 funcional, a uma aparente cura para o HIV-1 (GUPTA et al, 2019;XU et al;2017), isso porque, as células sanguíneas nulas do CCR5 são amplamente resistentes à entrada do vírus (XU et al, 2019).…”