Fast Facts: Gene Therapy

L. Popplewell, R. Herzog

Description

Gene therapy has emerged as a discipline in medicine that can provide treatments for diseases that have no other therapies available, save lives of patients for whom there is no other hope and replace suboptimal treatments with lasting cures. 'Fast Facts: Gene Therapy' provides an overview of the field, looking at the main vector systems used to transfer the therapeutic gene constructs, the molecular mechanisms and the history of gene therapy, as well as the safety and ethical considerations of this important advance. Multiple examples of diseases that are already successfully treated with gene therapy are given, with discussion of treatments that hold promise for the future. This book will be informative and of value to health professionals, researchers, students and anyone with an interest in this exciting and fast-moving area. Contents: • Principles of gene therapy • Gene therapy techniques • Ethical and safety considerations • Gene therapies with proven clinical efficacy • Genome editing • Research directions – the next wave of treatments

Informations

• Publié par: S. Karger AG
• Date de parution: 24 avril 2020
• Nombre de lectures: 0
• EAN13: 9783318066678
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Gene Therapy

Roland W Herzog PhD Professor of Pediatrics Riley Children s Foundation Professor of Immunology Director, Gene and Cell Therapy Program Herman B Wells Center for Pediatric Research Indiana University, Indianapolis Indiana, USA

Linda Popplewell PhD Lecturer in Biomedical Sciences Department of Biological Sciences Centre for Biomedical Sciences/Centre of Gene and Cell Therapy Royal Holloway University of London London, UK
Linda Popplewell acknowledges the contribution of Pradeep Harish and James T March, both members of her research group, to this book.
Declaration of Independence
This book is as balanced and as practical as we can make it.
Ideas for improvement are always welcome: [e-mail]
Fast Facts: Gene Therapy
First published 2020
Text 2020 Roland W Herzog, Linda Popplewell 2020 in this edition S. Karger Publishers Ltd
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A CIP record for this title is available from the British Library.
ISBN 978-3-318-06666-1 eISBN 978-3-318-06668-5
Herzog RW (Roland W)
Fast Facts: Gene Therapy/
Roland W Herzog, Linda Popplewell
Medical illustrations by Graeme Chambers. Typesetting by S. Karger Publishers Ltd, Abingdon, UK. Printed in the UK with Xpedient Print.
List of abbreviations
Glossary
Introduction
Principles of gene therapy
Gene therapy techniques
Ethical and safety considerations
Gene therapies with proven clinical efficacy
Genome editing
Research directions - the next wave of treatments
Useful resources
Index
List of abbreviations
AAV: adeno-associated virus
ADA-SCID: adenosine deaminase deficiency-severe combined immunodeficiency
AO: antisense oligonucleotide
ASGCT: American Society of Gene and Cell Therapy
B-ALL: B-cell acute lymphoblastic leukemia
CAR: chimeric antigen receptor
cDNA: complementary DNA
CGD: chronic granulomatous disease
CNS: central nervous system
CpG: cytosine-phosphate-guanine
CRISPR: clustered regularly interspaced short palindromic repeat
CRS: cytokine release syndrome
CSS: cryptic splice site
CTL: cytotoxic T lymphocyte
DLBCL: diffuse large B-cell lymphoma
DMD: Duchenne muscular dystrophy
DSB: double-strand break
EMA: European Medicines Agency
ERT: enzyme replacement therapy
FDA: (US) Food and Drug Administration
GSD: glycogen storage disease
GTMP: gene therapy medicinal product
HDR: homology-directed repair
HLA: human leukocyte antigen
HSC: hematopoietic stem cell
HSV: herpes simplex virus
IDLV: integration-deficient lentiviral vector
ITR: inverted terminal repeat
HSV: herpes simplex virus
lcnRNA: long non-coding RNA
IDLV: integration-deficient lentiviral vector
ITR: inverted terminal repeat
LTR: long terminal repeat
MHC: major histocompatibility complex
MRI: magnetic resonance imaging
miRNA: microRNA
mRNA: messenger RNA
NAb: neutralizing antibody
NHEJ: non-homologous end joining
NK: natural killer
NMD: nonsense-mediated decay
PTC: premature termination codon
RAC: Recombinant DNA Advisory Committee
RCR: replication-competent retrovirus
RFS: relapse-free survival
RISC: RNA-interfering silencing complex
SCD: sickle cell disease
SCID: severe combined immune deficiency
shRNA: short hairpin RNA
SIN: self-inactivating
siRNA: small interfering RNA
TALE: transcription activator-like effector
TALEN: transcription activator-like effector nuclease
Treg: regulatory T cell
UTR: untranslated region
WASP: Wiskott-Aldrich syndrome protein
XLMTM: X-linked myotubular myopathy
ZF : zinc finger
ZFN: zinc finger nuclease
Glossary
3 /5 untranslated region: portion of mRNA from the end to the position of the first (5 ) or last (3 ) codon used in translation
Antisense oligonucleotides: small pieces of RNA or DNA that can bind to specific RNA molecules and block transcription or translation or induce exon skipping or alternative splicing
CAR-T cells: T cells genetically engineered to express a specific chimeric antigen receptor to recognize an antigen on a tumor cell surface
Complementary DNA: DNA copy of an mRNA molecule produced by the enzyme reverse transcriptase
Dominant negative mutation: gene mutation for which the gene product adversely affects the usual gene product within the same cell, usually because it can still interact with the same elements as the wild-type product, but block some aspect of its function
Endonuclease: enzyme that cleaves the phosphodiester bond in a polynucleotide chain
Episome: a genetic element in bacteria that originates outside the host, in a virus or another bacterium, that can replicate free in the cytoplasm or can be inserted into the main bacterial chromosome and replicate with the chromosome
Exon: coding region of a gene that will be translated into a protein
Exon skipping: RNA splicing to avoid faulty or misaligned sections of genetic code so that a truncated but functional protein can be produced
Frameshift mutation: insertion or deletion of nucleotides into or from protein-coding DNA in which the number of added/deleted nucleotides is not divisible by three and so there is a shift in the reading of the triplet mRNA codons
Gain-of-function mutation: genetic mutation that gives the encoded protein new or enhanced activity
HLA: gene complex in humans that encodes the MHC proteins. There are three major and three minor MHC class I proteins (HLA-A, -B and -C [major] and -E, -F and -G [minor]) and three major and two minor class II proteins (HLA-DP, -DQ and -DR [major] and -DM and -DO [minor]). HLAs encoding MHC class III proteins encode elements of the complement system
Indel: genetic mutation in which there is a length difference between two alleles that has arisen as a consequence of either a sequence insertion or deletion (see also frameshift mutation)
Intron: a nucleotide sequence within a gene that is removed by splicing in the processing of precursor mRNA to mature mRNA
Knockdown: a process of deactivating or suppressing a gene; knockdown can be partial or complete, and can be reversible
Knockout: total removal or permanent deactivation of a gene
Long non-coding RNA: a sequence of more than 200 nucleotides encoded at loci between genes or overlapping with genes; most are transcribed, capped and spliced. Some roles, such as transcriptional regulation and epigenetic modification, are known, but many effects are unknown
Loss-of-function mutation: genetic mutation that reduces or abolishes the activity of the encoded protein
MHC: gene complex (known as HLA in humans) that encodes the MHC proteins (see also HLA)
MicroRNA: small regions of non-coding RNA (18-28 nucleotides) involved in transcriptional regulation
Monogenic: involving a single gene
Nonsense-mediated decay: quality-control mechanism through which aberrant newly synthesized mRNA that has a premature termination codon is degraded to avoid the production of a truncated and potentially disease-causing protein
Polygenic: involving several genes
Premature termination codon: mutation in a nucleotide sequence that results in an early codon that stops translation of the mRNA to protein
RNA interference: process of gene silencing through which double-stranded RNA molecules in a cell s cytoplasm are cleaved into siRNAs, which are then bound in a multiprotein complex (the RNA-induced silencing complex). Here, the RNA strands are separated, one strand is integrated in the RISC and the complementary strand guides and aligns the RISC to the target mRNA, which is cleaved and degraded
Short hairpin RNA: artificial RNA with a tight hairpin turn that can be used to silence a gene in the process of RNA interference
Small interfering RNA: short fragment of RNA (usually 21-25 nucleotides), produced from double-strand RNA or hairpin-looped RNA, that can cause gene silencing - see RNA interference
Steric hindrance: effect of molecular congestion on the speed of a chemical reaction
Transcription: first step in gene expression in which the DNA sequence of a gene is copied via RNA polymerases that link nucleotides to produce an RNA strand
Transcription factor: protein that binds to genetic sequence