- N Engl J Med 2022; 386:596-598
Clonal hematopoiesis of indeterminate potential (CHIP) is relatively common in older persons and is a risk factor for malignant blood conditions and cardiovascular disease. A recent study of a zebrafish model provides insight into how CHIP may evolve and implicates a positive feedback cycle.
- N Engl J Med 2022; 386:488-490
β-Thalassemia results from insufficient production of the hemoglobin subunit β-globin (β+) or from the absence of β-globin (β0). Low levels of adult hemoglobin (HbA, or α2β2 ) are exacerbated by excess free α-globin chains in erythroid cells, leading to dyserythropoiesis and shortening red-cell...
- N Engl J Med 2022; 386:415-427
Of 23 patients with transfusion-dependent β-thalassemia who received gene-transfected autologous hematopoietic cells, 91% became transfusion independent; the remaining 2 patients had a low level of engraftment of vector-expressing cells. With a median of 29.5 months of follow-up, the average hemoglobin level was 11.7 g per deciliter.
- N Engl J Med 2022; 386:188-190
A recent study involving murine stem cells showed a recapitulation of the entire female germline life cycle, which resulted in fertilizable mouse oocytes in culture. Among approximately 200 resultant two-cell embryos transferred into pseudopregnant dams, 5% resulted in live offspring.
- N Engl J Med 2021; 385:2003-2004
Hurler syndrome (mucopolysaccharidosis type I, Hurler variant [MPSIH]) is caused by autosomal recessive mutations in IDUA, leading to absent α-L -iduronidase (IDUA) expression. Deficient clearance of glycosaminoglycans (GAGs) leads to profound systemic manifestations, including neurocognitive impairment. IDUA can be endocytosed from the blood, and enzyme-replacement therapy is...
- N Engl J Med 2021; 385:1929-1940
Eight patients with Hurler syndrome who lacked suitable allogeneic donors received autologous hematopoietic stem and progenitor cells transduced ex vivo with an α-L-iduronidase–encoding lentiviral vector. This therapy resulted in extensive metabolic correction in peripheral tissues and the central nervous system.
- N Engl J Med 2021; 385:847-849
Engineering a model of the developing heart with stem cells has proved challenging. A recent study, however, provides a foundation — a single-chambered “cardioid” — for the development of such a model.
- N Engl J Med 2021; 384:2039-2052
DNA mutations occur in nearly every tissue throughout the human life span and accumulate at various rates in different tissues according to intrinsic and extrinsic factors. If a mutated clone acquires features that confer a competitive advantage, clonal dominance can emerge. Such alterations can have functional consequences and cause disease.
- N Engl J Med 2021; 384:2002-2013
Fifty patients in the United States and the United Kingdom underwent HSCT with CD34+ cells transduced with a replication-defective lentivirus bearing ADA . At 24 months, all the patients were alive, and event-free survival was 96.7% among the U.S. patients and 95% among the U.K. patients. Only two patients...
- N Engl J Med 2021; 384:1956-1958
A recent preclinical study provides support for the use of gene editing to circumvent the effects of mutations that cause congenital neutropenia. The authors also generated a mouse model of the disease.
- N Engl J Med 2021; 384:1766-1768
With age, the genomes within our cells accrue epigenetic marks that change gene expression. A recent study shows that age-associated epigenetic changes in retinal ganglion cells in a mouse model of glaucoma can be reversed and that vision can, to some extent, be restored.
- N Engl J Med 2021; 384:205-215
The switch from fetal to adult hemoglobin expression in humans is related to the active repression of HbF expression by BCL11A. A self-inactivating lentivirus vector with a short hairpin RNA designed to interfere with BCL11A expression was inserted into autologous hematopoietic stem cells of patients with...
- N Engl J Med 2020; 383:80-82
A study of genetically manipulated mouse models has shown that ultradian cycles of expression of a particular protein influence specification of cell type in the pancreas, a finding that has implications for understanding beta-cell identity and function.
- N Engl J Med 2020; 382:1926-1932
Dopaminergic progenitor cells that were derived from a patient’s induced pluripotent stem cells were implanted bilaterally in the putamen. Clinical and PET studies suggested survival of the cells and clinical stability over a period of 24 months, without dyskinesias.
- N Engl J Med 2020; 382:1660-1662
There has been much ado about the use of stem cells to replace cardiomyocytes after myocardial infarction. A recent study suggests that an immune response underlies benefit that had previously been attributed to stem cells.
- N Engl J Med 2019; 381:1681-1683
Placental health is critical to fetal health, but modeling the placenta is difficult. A recent study shows that both human and porcine stem-cell cultures can, in fact, be efficiently differentiated into trophoblasts and also converted into trophoblast stem cells.
- N Engl J Med 2019; 381:1240-1247
A young man with HIV infection and acute lymphoblastic leukemia, both in remission, underwent bone marrow transplantation with donor stem cells, a minority of which had undergone disruption of the CCR5 gene. The manipulated cells engrafted. Only a small percentage of the CD4+ cells carried the disrupted gene,...
- N Engl J Med 2019; 381:1281-1283
A new form of gene therapy termed genetic editing or gene targeting has become possible owing to advances in genetic engineering technology.1 The intent of genetic editing is to alter the DNA code in cells with single base-pair specificity, and thus it can be considered to be an...
- N Engl J Med 2019; 380:2268-2270
Ectopic calcification results in mineralization of soft tissues such as the heart valves, blood vessels, and skeletal muscle. A recent study provides a genetic explanation of underlying tissue susceptibility to this process.
- N Engl J Med 2019; 380:2237-2245
Cancers arise in tissues that can replicate and self-renew. Like normal tissues, cancers can replenish themselves, grow, and metastasize because of stem cells that are similar to normal stem cells but seem to respond less well to environmental stop signals in their niche. Therapy that targets cancer stem cells may...