Methods for inactivating in a
cell a
mutant allele of the
elastase, neutrophil expressed
gene (ELANE
gene)
gene having a
mutation associated with severe congenital
neutropenia (SCN) or cyclic
neutropenia (CyN) and which
cell is heterozygous at one or more polymorphic sites selected from the group consisting of: rs10424470, rs4807932, rs10414837, rs376107533, rs3761010, rs10413889, rs3761007, rs10409474, rs3761005, rs351107, rs3761001, rs740021, rs781452480, rs371057361, rs570466264, rs1041904080, rs7250194, rs17216649, rs199720952, rs6510983, rs17223066, rs7255385, rs112639467, rs141213775, rs28591229, rs10469327, rs3834645, rs1683564, rs71335276, and rs8107095, the method comprisingintroducing to the
cell a composition comprising:a
CRISPR nuclease or a sequence encoding the
CRISPR nuclease; anda first
RNA molecule comprising a guide sequence portion having 17-30 nucleotides,wherein a complex of the
CRISPR nuclease and the first
RNA molecule affects a
double strand break in the
mutant allele of the ELANE genethe method optionally further comprising introduction of a second
RNA molecule comprising a guide sequence portion capable of complexing with a CRISPR nuclease, wherein the complex of the second
RNA molecule and CRISPR nuclease affects a second
double strand break in the ELANE gene.