A versatile reporter system for multiplexed screening of effective epigenome editors

Azcona, Maria Silvia Roman; Fang, Yongxing; Carusillo, Antonio; Cathomen, Toni; Mussolino, Claudio

doi:10.1038/s41596-020-0380-y

Cited by 2 publications

(1 citation statement)

References 18 publications

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“…Therefore, the technological advancement offered by DEMs might be of great value as they combine in a single molecule the ability to alter the epigenome both at DNA and histone levels. While we have shown that these effectors can be efficiently used to silence the expression of genes that promote HIV infection (Mlambo et al, 2018) or T cells exhaustion (Roman Azcona et al, 2020), it will be interesting to prove their potential in silencing repressors of γ-globin gene, such as BCL11A, to promote HBG reactivation. Even though an approach that results in broad BCLA11A suppression is likely detrimental for the crucial role of this transcription factor in non-erythroid cells (Luc et al, 2016), the recent evidence that this gene can be ablated in an erythroid-specific fashion (Brendel et al, 2016) provides a new opportunity to be explored in the epigenome editing field.…”

Section: Gene Therapymentioning

confidence: 99%

Recent Approaches for Manipulating Globin Gene Expression in Treating Hemoglobinopathies

Mussolino

Strouboulis

2021

Front. Genome Ed.

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Tissue oxygenation throughout life depends on the activity of hemoglobin (Hb) one of the hemeproteins that binds oxygen in the lungs and secures its delivery throughout the body. Hb is composed of four monomers encoded by eight different genes the expression of which is tightly regulated during development, resulting in the formation of distinct hemoglobin tetramers in each developmental stage. Mutations that alter hemoglobin structure or its regulated expression result in a large group of diseases typically referred to as hemoglobinopathies that are amongst the most common genetic defects worldwide. Unprecedented efforts in the last decades have partially unraveled the complex mechanisms that control globin gene expression throughout development. In addition, genome wide association studies have revealed protective genetic traits capable of ameliorating the clinical manifestations of severe hemoglobinopathies. This knowledge has fueled the exploration of innovative therapeutic approaches aimed at modifying the genome or the epigenome of the affected cells to either restore hemoglobin function or to mimic the effect of protective traits. Here we describe the key steps that control the switch in gene expression that concerns the different globin genes during development and highlight the latest efforts in altering globin regulation for therapeutic purposes.

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