TY - JOUR
T1 - Revolutionising healing
T2 - Gene Editing's breakthrough against sickle cell disease
AU - Dimitrievska, Marija
AU - Bansal, Dravie
AU - Vitale, Marta
AU - Strouboulis, John
AU - Miccio, Annarita
AU - Nicolaides, Kypros H
AU - El Hoss, Sara
AU - Shangaris, Panicos
AU - Jacków-Malinowska, Joanna
N1 - Funding Information:
SEH received funding from the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie grant agreement number 101024970 . PS is supported by a Fetal Medicine Foundation Senior Clinical Lectureship and grants from the Fetal Medicine Foundation . KHN is supported by the Fetal Medicine Foundation . JS is funded by DBA UK Diamond Blackfan Anaemia Charity and the European Commission . AM is funded by the European Research Council . Gene editing work is supported by CureEB fundation to JJM.
Publisher Copyright:
© 2024 The Authors
PY - 2024/5
Y1 - 2024/5
N2 - Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point mutation in the β-globin gene. Despite the availability of several FDA-approved medications for symptomatic relief, allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative option, underscoring a persistent need for novel treatments. This review delves into the growing field of gene editing, particularly the extensive research focused on curing haemoglobinopathies like SCD. We examine the use of techniques such as CRISPR-Cas9 and homology-directed repair, base editing, and prime editing to either correct the pathogenic variant into a non-pathogenic or wild-type one or augment fetal haemoglobin (HbF) production. The article elucidates ways to optimize these tools for efficacious gene editing with minimal off-target effects and offers insights into their effective delivery into cells. Furthermore, we explore clinical trials involving alternative SCD treatment strategies, such as LentiGlobin therapy and autologous HSCT, distilling the current findings. This review consolidates vital information for the clinical translation of gene editing for SCD, providing strategic insights for investigators eager to further the development of gene editing for SCD.
AB - Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point mutation in the β-globin gene. Despite the availability of several FDA-approved medications for symptomatic relief, allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative option, underscoring a persistent need for novel treatments. This review delves into the growing field of gene editing, particularly the extensive research focused on curing haemoglobinopathies like SCD. We examine the use of techniques such as CRISPR-Cas9 and homology-directed repair, base editing, and prime editing to either correct the pathogenic variant into a non-pathogenic or wild-type one or augment fetal haemoglobin (HbF) production. The article elucidates ways to optimize these tools for efficacious gene editing with minimal off-target effects and offers insights into their effective delivery into cells. Furthermore, we explore clinical trials involving alternative SCD treatment strategies, such as LentiGlobin therapy and autologous HSCT, distilling the current findings. This review consolidates vital information for the clinical translation of gene editing for SCD, providing strategic insights for investigators eager to further the development of gene editing for SCD.
UR - http://www.scopus.com/inward/record.url?scp=85188004181&partnerID=8YFLogxK
U2 - 10.1016/j.blre.2024.101185
DO - 10.1016/j.blre.2024.101185
M3 - Review article
C2 - 38493007
SN - 0268-960X
VL - 65
SP - 101185
JO - Blood Reviews
JF - Blood Reviews
M1 - 101185
ER -