Allele-specific gene suppression

An oligonucleotide that suppresses the expression of an allele carrying a dominant mutation that causes hereditary sensory neuropathy type I (HSN1), wherein the suppression takes place through hybridisation of said oligonucleotide to the DNA of said allele or to an RNA transcript of said allele, and which either does not suppress the expression of a wild-type allele not containing the dominant mutation or suppresses the expression of said wild-type allele to a lesser extent than it suppresses the expression of the dominant mutant allele, wherein the dominant mutation is in the serine palmitoyltransferase long chain subunit 1 (SPTLC1) gene, and wherein (i) the oligonucleotide is double-stranded;

• (ii) the oligonucleotide is a single-stranded antisense oligonucleotide (AON) comprising both DNA and RNA bases;
• or (iii) the oligonucleotide is a guide RNA comprising a guide sequence that hybridises to the site of said dominant mutation and targets a CRISPR-Cas enzyme to said site.