{
  "abstract": "Technologies underlying nucleic acid therapies (NATs) have significantly advanced leading to successful approvals of NAT drugs across various diseases. Notably, successes in antisense oligonucleotide (ASO) therapies have dominated approvals in rare diseases. Many patients with a rare genetic disease stand to benefit from these treatments and, as underlying technologies continue to advance, a critical barrier to care is the equitable selection of patients. Landmark progress in genomic health care uniquely positions the UK to develop a national NATs patient-selection infrastructure and UPNAT has been launched, in part, to meet this goal by developing guidelines to assess potential patients for NAT development and treatment, using ASO therapies as a pilot. We present the first UK focused guidelines, developed by a panel of UK-based multi-disciplinary experts, that allow systematic assessment of criteria across disease, gene, variant and individual patient subgroups, incorporating the recently published N1C variant guidelines. Guidelines enable rapid prioritisation of promising targets and identification of barriers stalling ASO development and will be adaptable to fast-paced technological advances in this field. Application of guidelines is underway in real-world settings through the assessment of genomic and clinical data within both highly specialised NHS clinics and the Genomics England National Genomic Research Library.",
  "authors": [
    {
      "affiliations": [
        "Great Ormond Street Institute of Child Health, University College London, London, UK"
      ],
      "name": "Ella F Whittle"
    },
    {
      "affiliations": [
        "Great Ormond Street Institute of Child Health, University College London, London, UK",
        "Department of Neuromuscular Diseases, Queen Square Institute of Neurology, UCL, London WC1N 1PJ, UK"
      ],
      "name": "Kylie-Ann Montgomery"
    },
    {
      "affiliations": [
        "Great Ormond Street Institute of Child Health, University College London, London, UK"
      ],
      "name": "Catherine Ryan"
    },
    {
      "affiliations": [
        "Department of Clinical Genetics, Great Ormond Street Hospital for Children, London, UK"
      ],
      "name": "Emma Clement"
    },
    {
      "affiliations": [
        "Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK",
        "Genomics England, One Canada Square, London E14 5AB"
      ],
      "name": "Nour Elkhateeb"
    },
    {
      "affiliations": [
        "Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health/Department of Neurology, Great Ormond Street Hospital for Children, London, UK"
      ],
      "name": "Manju A Kurian"
    },
    {
      "affiliations": [
        "UCL Institute of Ophthalmology 11-43 Bath Street, London EC1V 9EL"
      ],
      "name": "Jacqui van der Spuy"
    },
    {
      "affiliations": [
        "Institute of Developmental and Regenerative Medicine, Department of Paediatrics, University of Oxford, Oxford OX3 7TY, UK"
      ],
      "name": "Stephan J Sanders"
    },
    {
      "affiliations": [
        "Genomics England, One Canada Square, London E14 5AB"
      ],
      "name": "Ana Lisa Tavares"
    },
    {
      "affiliations": [
        "Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK"
      ],
      "name": "Jenny C Taylor"
    },
    {
      "affiliations": [
        "Clinical Genetics, Birmingham Women’s and Children’s Hospital NHS Foundation Trust, Birmingham, UK/Clinical Sciences Department, University of Birmingham, Birmingham, UK"
      ],
      "name": "Hannah Titheradge"
    },
    {
      "affiliations": [
        "MRC Nucleic Acid Therapy Accelerator, Research Complex at Harwell, UK"
      ],
      "name": "Nick Lench"
    },
    {
      "affiliations": [
        "Institute of Developmental and Regenerative Medicine, Department of Paediatrics, University of Oxford, Oxford OX3 7TY, UK"
      ],
      "name": "Carlo Rinaldi"
    },
    {
      "affiliations": [
        "Great Ormond Street Institute of Child Health, University College London, London, UK"
      ],
      "name": "Francesco Muntoni"
    },
    {
      "affiliations": [
        "Great Ormond Street Institute of Child Health, University College London, London, UK"
      ],
      "name": "Haiyan Zhou"
    },
    {
      "affiliations": [
        "UCL Institute of Ophthalmology 11-43 Bath Street, London EC1V 9EL"
      ],
      "name": "Alice Davidson"
    },
    {
      "affiliations": [
        "Great Ormond Street Institute of Child Health, University College London, London, UK",
        "UK Dementia Research Institute at The University of Cambridge, Cambridge, UK/Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK"
      ],
      "name": "Mina Ryten"
    },
    {
      "affiliations": [
        "Great Ormond Street Institute of Child Health, University College London, London, UK",
        "Department of Neuromuscular Diseases, Queen Square Institute of Neurology, UCL, London WC1N 1PJ, UK",
        "Department of Clinical Genetics, Great Ormond Street Hospital for Children, London, UK",
        "Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK",
        "Genomics England, One Canada Square, London E14 5AB",
        "Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, Great Ormond Street Institute of Child Health/Department of Neurology, Great Ormond Street Hospital for Children, London, UK",
        "UCL Institute of Ophthalmology 11-43 Bath Street, London EC1V 9EL",
        "Institute of Developmental and Regenerative Medicine, Department of Paediatrics, University of Oxford, Oxford OX3 7TY, UK",
        "Centre for Human Genetics and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, UK",
        "Clinical Genetics, Birmingham Women’s and Children’s Hospital NHS Foundation Trust, Birmingham, UK/Clinical Sciences Department, University of Birmingham, Birmingham, UK",
        "MRC Nucleic Acid Therapy Accelerator, Research Complex at Harwell, UK",
        "UK Dementia Research Institute at The University of Cambridge, Cambridge, UK/Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, University of Cambridge, Cambridge, UK"
      ],
      "name": "on behalf of the UPNAT consortium"
    }
  ],
  "title": "O6 The UK platform for nucleic acid therapies – target selection guidelines",
  "uid": "de7eae1f-ebd2-58c1-b576-8e90e4f4bc20"
}