Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease DOI Creative Commons
Martijn P. T. Ernst, Mike Broeders,

Pablo Herrero-Hernandez

et al.

Molecular Therapy — Methods & Clinical Development, Journal Year: 2020, Volume and Issue: 18, P. 532 - 557

Published: July 4, 2020

We present an overview of clinical trials involving gene editing using clustered interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), or zinc finger (ZFNs) and discuss the underlying mechanisms. In cancer immunotherapy, is applied ex vivo in T cells, transgenic cell receptor (tTCR)-T chimeric antigen (CAR)-T cells to improve adoptive therapy for multiple types. This involves knockouts immune checkpoint regulators such as PD-1, components endogenous TCR histocompatibility leukocyte (HLA) complex generate universal allogeneic CAR-T CD7 prevent self-destruction therapy. cervix carcinoma caused by human papillomavirus (HPV), E6 E7 genes are disrupted topically machinery. HIV infection, CCR5 co-receptor HIV-resistant hematopoietic stem cells. β-thalassemia sickle disease, engineered induce production fetal hemoglobin. AAV-mediated exploit liver systemic therapeutic proteins hemophilia mucopolysaccharidoses, eye restore splicing CEP920 Leber's congenital amaurosis. Close consideration safety aspects education stakeholders will be essential a successful implementation technology clinic.

Language: Английский

The spatial epidemiology of sickle-cell anaemia in India DOI Creative Commons
Carinna Hockham, Samir Bhatt, Roshan Colah

et al.

Scientific Reports, Journal Year: 2018, Volume and Issue: 8(1)

Published: Nov. 30, 2018

Abstract Sickle-cell anaemia (SCA) is a neglected chronic disorder of increasing global health importance, with India estimated to have the second highest burden disease. In country, SCA particularly prevalent in scheduled populations, which comprise most socioeconomically disadvantaged communities. We compiled geodatabase substantial number surveys carried out over last decade. Using generalised additive models and bootstrapping methods, we generated first India-specific model-based map sickle-cell allele frequency accounts for district-level distribution non-scheduled populations. Where possible, derived state- estimates newborns 2020 two groups. Through inclusion an additional 158 data points 1.3 million individuals, considerably increased amount our mapping evidence-base compared previous studies. Highest predicted frequencies up 10% spanned central India, whilst hotspot ~12% was observed Jammu Kashmir. Evidence heavily biased towards populations remained limited can lead considerable uncertainties newborn at national state level. This has important implications policy planning. By taking population composition into account, maps that better reflect complex epidemiology turn provide more reliable its vast country. work supported by European Union’s Seventh Framework Programme (FP7//2007–2013)/European Research Council [268904 – DIVERSITY]; Newton-Bhabha Fund [227756052 CH]

Language: Английский

Citations

101
Techniques for the Detection of Sickle Cell Disease: A Review DOI Creative Commons

Wjdan A. Arishi,

Hani A. Alhadrami, Mohammed Zourob

et al.

Micromachines, Journal Year: 2021, Volume and Issue: 12(5), P. 519 - 519

Published: May 5, 2021

Sickle cell disease (SCD) is a widespread caused by mutation in the beta-globin gene that leads to production of abnormal hemoglobin called S. The inheritance could be homozygous or heterozygous combined with another mutation. SCD can characterized presence dense, sickled cells causes hemolysis blood cells, anemia, painful episodes, organ damage, and some cases death. Early detection help reduce mortality manage effectively. Therefore, different techniques have been developed detect sickle carrier states high sensitivity specificity. These screening tests such as complete count, peripheral smears, sickling test; confirmatory separation techniques; genetic tests, which are more expensive need done centralized labs highly skilled personnel. However, advanced portable point care provide low-cost, simple, user-friendly device for detecting SCD, instance coupling solubility devices, using smartphone microscopic classifications, image processing techniques, rapid immunoassays, sensor-based platforms. This review provides an overview current emerging highlights potential methods applied early diagnosis SCD.

Language: Английский

Citations

91
Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial DOI
Jo Howard, Kenneth I. Ataga,

Robert C. Brown

et al.

The Lancet Haematology, Journal Year: 2021, Volume and Issue: 8(5), P. e323 - e333

Published: April 7, 2021

Language: Английский

Citations

90
In Vivo Outcome of Homology-Directed Repair at the HBB Gene in HSC Using Alternative Donor Template Delivery Methods DOI Creative Commons
Sowmya Pattabhi,

S. N. Lotti,

Mason P. Berger

et al.

Molecular Therapy — Nucleic Acids, Journal Year: 2019, Volume and Issue: 17, P. 277 - 288

Published: June 8, 2019

Gene editing following designer nuclease cleavage in the presence of a DNA donor template can revert mutations disease-causing genes. For optimal benefit, reversion point mutation HBB leading to sickle cell disease (SCD) would permit precise homology-directed repair (HDR) while concurrently limiting on-target non-homologous end joining (NHEJ)-based disruption. In this study, we directly compared relative efficiency co-delivery novel CRISPR/Cas9 ribonucleoprotein targeting association with recombinant adeno-associated virus 6 (rAAV6) versus single-stranded oligodeoxynucleotides (ssODNs) introduce (GTC or GTG; encoding E6V) silent change (GAA; E6optE) human CD34

Language: Английский

Citations

85
Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease DOI Creative Commons
Martijn P. T. Ernst, Mike Broeders,

Pablo Herrero-Hernandez

et al.

Molecular Therapy — Methods & Clinical Development, Journal Year: 2020, Volume and Issue: 18, P. 532 - 557

Published: July 4, 2020

We present an overview of clinical trials involving gene editing using clustered interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), or zinc finger (ZFNs) and discuss the underlying mechanisms. In cancer immunotherapy, is applied ex vivo in T cells, transgenic cell receptor (tTCR)-T chimeric antigen (CAR)-T cells to improve adoptive therapy for multiple types. This involves knockouts immune checkpoint regulators such as PD-1, components endogenous TCR histocompatibility leukocyte (HLA) complex generate universal allogeneic CAR-T CD7 prevent self-destruction therapy. cervix carcinoma caused by human papillomavirus (HPV), E6 E7 genes are disrupted topically machinery. HIV infection, CCR5 co-receptor HIV-resistant hematopoietic stem cells. β-thalassemia sickle disease, engineered induce production fetal hemoglobin. AAV-mediated exploit liver systemic therapeutic proteins hemophilia mucopolysaccharidoses, eye restore splicing CEP920 Leber's congenital amaurosis. Close consideration safety aspects education stakeholders will be essential a successful implementation technology clinic.

Language: Английский

Citations

80