The future of sickle cell disease therapeutics rests in genomics

Abstract

ABSTRACT Sickle cell disease (SCD) is the most-common monogenic recessive disease in humans, annually affecting almost 300,000 newborns worldwide, 75% of whom live in Africa. Genomics research can accelerate the development of curative therapies for SCD in three ways. First, research should explore the missing heritability of foetal haemoglobin (HbF) – the strongest known modifier of SCD clinical expression – among highly genetically heterogenous and understudied African populations, to provide novel therapeutics targets for HbF induction. Second, SCD research should invest in RNA therapies, either by using microRNA to target the production of HbF proteins by binding to the transcription machinery in a cell, or by directly mediating production of HbF or adult haemoglobin through injection of messenger RNA. Third, investigators should aim to identify currently unknown genetic risk factors for SCD cardiovascular complications, which will address mortality, particularly in adults. Now is the time for global research programs to uncover genomic keys to unlock SCD therapeutics.