Rational macromolecular design reveals principles of ribonucleoprotein delivery for gene editing

Introduction: Genome editing in human hematopoietic stem and progenitor cells (HSPCs) holds the potential to elucidate gene-function relationships through precise genetic manipulation and offers a promising avenue for curing currently intractable hematological disorders. The CRISPR-Cas system has revolutionized genome engineering; however, its clinical application has been limited by challenges in delivery and target specificity. These obstacles may be overcome through biochemical engineering of the CRISPR-Cas system, incorporating cell-penetrating peptide (CPP) domains and specificity ligands.