Extended Data Fig. 5: Gene expression of molecules involved in the regulation of hFVIII-SQ RNA expression.
a) Down-regulation in Participant 15 (low-responder) of molecules involved in positive regulation of transcriptional pathways. b) Upregulation in Participant 15 (low-responder) of zinc and copper metabolic pathway negatively correlated with liver hFVIII-SQ RNA levels. c) Expression levels of transcription factors predicted to bind to the hybrid liver-specific promoter (HLP) in AAV5-hFVIII-SQ. TPM, transcripts per million. Gene names and descriptions: a. Genes clustered in the regulation of transcription, DNA templated pathway. CKS1B, CDC28 protein kinase regulatory subunit 1B; DAB2, Dab, mitogen-responsive phosphoprotein, homolog 2 (Drosophila); DDIT3, DNA-damage-inducible transcript 3; ELK3, ELK3, ETS-domain protein (SRF accessory protein 2); EHF, ets homologous factor; KLF6, Kruppel-like factor 6; PHF5A, plant homeodomain (PHD) finger protein 5A; SMAD3, SMAD family member 3; SS18L1, synovial sarcoma translocation gene on chromosome 18-like 1; TAF8, TAF8 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 43 kDa; APBB1, amyloid beta (A4) precursor protein-binding, family B, member 1 (Fe65); BMP10, bone morphogenetic protein 10; CALCOCO1, calcium binding and coiled-coil domain 1; CAPN3, calpain 3, (p94); CEP290, centrosomal protein 290 kDa; CDK2, cyclin-dependent kinase 2; CRLF3, cytokine receptor-like factor 3; ING5, inhibitor of growth family, member 5; IKBKB, inhibitor of kappa light polypeptide gene enhancer in B cells, kinase beta; IRF1, interferon regulatory factor 1; IRF6, interferon regulatory factor 6; MED17, mediator complex subunit 17; MAPRE3, microtubule-associated protein, RP/EB family, member 3; NUP85, nucleoporin 85 kDa; PLCB1, phospholipase C, beta 1 (phosphoinositide-specific); RNF187, ring finger protein 187; TGFB3, transforming growth factor, beta 3; TP53BP1, tumor protein p53 binding protein 1; ZBTB16, zinc finger and BTB domain containing 16. b. Genes clustered in the Zinc and Copper Metabolism pathway. MT1, metallothionein 1. c. Transcription factors predicted to bind to the HLP promoter in AAV5-hFVIII-SQ. CEBPa, CCAAT/enhancer-binding protein alpha; HNF1a, hepatocyte nuclear factor 1 alpha; HNF4a, hepatocyte nuclear factor 4 alpha.
