Development and IND-enabling studies of a novel Cas9 genome-edited autologous CD34 cell therapy to induce fetal hemoglobin for sickle cell disease.

Sickle cell disease (SCD) is a common, severe genetic blood disorder. Current pharmacotherapies are partially effective and allogeneic hematopoietic stem cell transplantation is associated with immune toxicities. Genome editing of patient hematopoietic stem cells (HSCs) to reactivate fetal hemoglobin (HbF) in erythroid progeny offers an alternative potentially curative approach to treat SCD.

Potent and uniform fetal hemoglobin induction via base editing.

Inducing fetal hemoglobin (HbF) in red blood cells can alleviate β-thalassemia and sickle cell disease. We compared five strategies in CD34 hematopoietic stem and progenitor cells, using either Cas9 nuclease or adenine base editors. The most potent modification was adenine base editor generation of γ-globin -175A>G.

Ex vivo prime editing of patient haematopoietic stem cells rescues sickle-cell disease phenotypes after engraftment in mice.

Sickle-cell disease (SCD) is caused by an A·T-to-T·A transversion mutation in the β-globin gene (HBB). Here we show that prime editing can correct the SCD allele (HBB) to wild type (HBB) at frequencies of 15%-41% in haematopoietic stem and progenitor cells (HSPCs) from patients with SCD. Seventeen weeks after transplantation into immunodeficient mice, prime-edited SCD HSPCs maintained HBB levels and displayed engraftment frequencies, haematopoietic differentiation and lineage maturation similar to those of unedited HSPCs from healthy donors.

The Clinical and Laboratory Profiles of Immunocompetent Patients With Short-Duration Fever With Neutropenia in a Tertiary Care Hospital in Pune, India.

Background Management of a febrile patient is based on understanding the pathophysiology of an abnormal temperature and temperature regulation, impacts of fever, and its treatment. In the current study, we aimed to characterize and compare the epidemiological, etiologic, microbiological, serological, clinical, and outcome traits of febrile patients with acute neutropenia admitted to a tertiary care center in Western Maharashtra. Methods Adult patients with a history of fever of less than two weeks' duration and without any immunosuppressive state were screened with predefined inclusion and exclusion criteria.

Study of Infections in Type 2 Diabetes Mellitus.

Unlabelled: Diabetes mellitus (DM) is a clinical syndrome associated with deficiency of insulin secretion or action. It is considered one of the largest emerging threats to health in the 21st century. Besides the classical complications of the disease, DM has been associated with reduced response of T cells, neutrophil function, and disorders of humoral immunity.