Gene Therapy in a Patient with Sickle Cell Disease

Badat, Mohsin; Davies, James O. J.

doi:10.1056/nejmc1704009

Cited by 21 publications

(3 citation statements)

References 8 publications

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“…The ex vivo , genetically modified CD34 + cells that include HSCs are infused back into the patient and the genetically modified cells engraft and subsequently produce hematopoietic cells expressing the therapeutic gene ( Figure 1 ). This ex vivo gene therapy principle has been shown to be efficacious in diseases such as severe combined immunodeficiency due to adenosine deaminase deficiency (ADA-SCID) (Aiuti et al, 2009 ), X-linked severe combined immunodeficiency (Hacein-Bey-Abina et al, 2002 , 2010 ; Pavel-Dinu et al, 2019 ) and more recently for hemoglobinopathies including SCD, conditions that require high levels of therapeutic gene expression to attain phenotypic rescue (Woods et al, 2006 ; Badat and Davies, 2017 ). Currently, departing from “classic” gene therapy, gene editing technology based on programmable nucleases is offering the perspective for changing the genome of HSCs with unprecedented specificity and accuracy.…”

Section: State-of-the-art Genome Engineering Of Hscsmentioning

confidence: 99%

Genomic Engineering in Human Hematopoietic Stem Cells: Hype or Hope?

et al. 2021

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Many gene editing techniques are developed and tested, yet, most of these are optimized for transformed cell lines, which differ from their primary cell counterparts in terms of transfectability, cell death propensity, differentiation capability, and chromatin accessibility to gene editing tools. Researchers are working to overcome the challenges associated with gene editing of primary cells, namely, at the level of improving the gene editing tool components, e.g., the use of modified single guide RNAs, more efficient delivery of Cas9 and RNA in the ribonucleoprotein of these cells. Despite these efforts, the low efficiency of proper gene editing in true primary cells is an obstacle that needs to be overcome in order to generate sufficiently high numbers of corrected cells for therapeutic use. In addition, many of the therapeutic candidate genes for gene editing are expressed in more mature blood cell lineages but not in the hematopoietic stem cells (HSCs), where they are tightly packed in heterochromatin, making them less accessible to gene editing enzymes. Bringing HSCs in proliferation is sometimes seen as a solution to overcome lack of chromatin access, but the induction of proliferation in HSCs often is associated with loss of stemness. The documented occurrences of off-target effects and, importantly, on-target side effects also raise important safety issues. In conclusion, many obstacles still remain to be overcome before gene editing in HSCs for gene correction purposes can be applied clinically. In this review, in a perspective way, we will discuss the challenges of researching and developing a novel genetic engineering therapy for monogenic blood and immune system disorders.

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Section: State-of-the-art Genome Engineering Of Hscsmentioning

confidence: 99%

Genomic Engineering in Human Hematopoietic Stem Cells: Hype or Hope?

et al. 2021

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“…В результате терапии биохимические параметры крови пришли в норму, и переливание эритроцитарной массы было прекращено на 88 сутки после трансплантации. Пациент был выписан на 50 сутки после трансплантации, и повторных госпитализаций, связанных с заболеванием, у него не было на протяжении более 15 месяцев [33].…”

Section: клеточная терапия рецессивного дистрофического буллезного эп...unclassified

Treatment of Genetic Diseases: Current Trends in the Development of Biomedical Cell Products

Rachinskaya¹,

Vodyakova²,

Мельникова³

et al. 2019

Biopreparaty. Profilaktika, diagnostika, lechenie

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Genetic diseases are often progressive in nature, and without proper treatment may result in disability or death. Difficulties with diagnosis of genetic diseases and lack of effective treatment are global public health challenges. Medical care for patients with genetic diseases is often confined to symptomatic and palliative care. Starting from the 2000s, great hopes have been placed on cell-based medicinal products (which are referred to as biomedical cell products in the Russian legislation) and gene therapy products. The aim of the study was to review current trends in the development of biomedical cell products for the treatment of genetic diseases. The paper focuses on cell-based products for the treatment of monogenic genetic diseases, such as severe combined immunodeficiency (SCID), recessive dystrophic epidermolysis bullosa (RDEB), beta-haemoglobinopathies, alpha-1-antitrypsin deficiency, haemophilia A, and Duchenne muscular dystrophy. Such drugs are being developed in many countries and are now entering preclinical and different stages of clinical trials. Products based on various types of viable cells, including differentiated cells, stem cells, induced pluripotent cells, as well as cells genetically modified ex vivo, may be developed for the treatment of one and the same disease. The main priority is the creation of such products that will obviate the need for replacement therapy or palliative care, and that will significantly increase life expectancy and quality of life.

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“…Adli (2018),Andreani, Verneau, Raoult, Levasseur, and La Scola (2018),Antwerpen et al (2015),Badat and Davies (2017),Demirci, Uchida, and Tisdale (2018),Eid and Mahfouz (2016),Gahl et al (2016),Green, Watson, and Collins (2015),Leboulch and Cavazzana (2017),Legendre et al (2018),Liu et al (2018),Moraes and Goes (2016), National Institutes of Health (2018),Nerlich and Hellsten (2004),Pevsner (2015),Piatek, Lenaghan, and Neal Stewart (2018),Ribeil et al (2017),Suravajhala, Kogelman, and Kadarmideen (2016),Yin et al (2014), andZhen et al (2015).…”

mentioning

confidence: 99%

Genomic Science—From 2001 to Present Day: What School Nurses Need to Know

2018

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Genetic science has made remarkable advances in the 21st century. As genetic and genomic sciences continue to expand, school nurses will become thoroughly immersed in data, information, and technology. As new diseases, treatments, and therapies are discovered, school nurses will need to implement and assess best practices for the complex and medically fragile student population. This article will discuss the top 10 recent discoveries in genomic science and how school nurses can use this information in clinical practice.

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Gene Therapy in a Patient with Sickle Cell Disease

Cited by 21 publications

References 8 publications

Genomic Engineering in Human Hematopoietic Stem Cells: Hype or Hope?

Genomic Engineering in Human Hematopoietic Stem Cells: Hype or Hope?

Treatment of Genetic Diseases: Current Trends in the Development of Biomedical Cell Products

Genomic Science—From 2001 to Present Day: What School Nurses Need to Know

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