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However, wild-type huntingtin (HTT) has important cellular functions, so the ideal strategy would selectively lower mutant HTT while sparing wild-type. HD patients were genotyped for heterozygosity at three SNP sites, before phasing each SNP allele to wild-type or mutant <jats:italic>HTT<\/jats:italic>. Primary <jats:italic>ex vivo<\/jats:italic> myeloid cells were isolated from heterozygous patients and transfected with SNP-targeted siRNA, using glucan particles taken up by phagocytosis. Highly selective mRNA knockdown was achieved when targeting each allele of rs362331 in exon 50 of the <jats:italic>HTT<\/jats:italic> transcript; this selectivity was also present on protein studies. However, similar selectivity was not observed when targeting rs362273 or rs362307. Furthermore, HD myeloid cells are hyper-reactive compared to control. Allele-selective suppression of either wild-type or mutant HTT produced a significant, equivalent reduction in the cytokine response of HD myeloid cells to LPS, suggesting that wild-type HTT has a novel immune function. We demonstrate a sequential therapeutic process comprising genotyping and mutant <jats:italic>HTT<\/jats:italic>-linkage of SNPs, followed by personalised allele-selective suppression in a small patient cohort. We further show that allele-selectivity in <jats:italic>ex vivo<\/jats:italic> patient cells is highly SNP-dependent, with implications for clinical trial target selection.<\/jats:p>","DOI":"10.1038\/srep46740","type":"journal-article","created":{"date-parts":[[2017,4,24]],"date-time":"2017-04-24T09:34:58Z","timestamp":1493026498000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Allele-Selective Suppression of Mutant Huntingtin in Primary Human Blood Cells"],"prefix":"10.1038","volume":"7","author":[{"given":"James R. 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