C-C chemokine receptor type 5 (CCR5) gene locus (CCR5 locus)

The C-C chemokine receptor type 5 (CCR5) gene locus is a genomic site targeted for therapeutic gene editing to treat lysosomal storage disorders and neurodegenerative conditions (UniProt P51681). This specific strategy involves using site-specific nucleases, such as Zinc Finger Nucleases (ZFNs), to insert a functional Glucocerebrosidase (GBA) gene (UniProt P04062) into the CCR5 locus while simultaneously disrupting the endogenous CCR5 gene (Sangamo Therapeutics). The CCR5 locus is utilized as a safe harbor because its loss is naturally occurring in humans (CCR5-delta32) and is generally well-tolerated, providing a stable environment for transgene expression without disrupting essential cellular functions (PubMed: PMC4350748). By knocking in GBA, the therapy aims to restore the activity of the acid beta-glucosidase enzyme, which is deficient in Gaucher disease and a major risk factor for Parkinson's disease (PubMed: 25158682). This dual-action approach provides a permanent source of the therapeutic enzyme while potentially conferring resistance to R5-tropic HIV-1 infection as a secondary benefit of the CCR5 knockout.

Other names

CCR5CD195CKR5CMKBR5C-C motif chemokine receptor 5 locusCCR5 safe harbor

Targeted genomic integration of a functional GBA1 gene and simultaneous disruption of the CCR5 coding sequence using site-specific endonucleases.