Disclosed herein are methods for producing red blood cells (RBCs) from a population of stem cells and/or progenitor cells. In at least one of the stem cells or progenitor cells, SH2B3 protein activity is decreased, SH2B3 mRNA level is decreased, and/or SH2B3 protein level is decreased. The methods provided herein permit the production of RBCs with increased quantity and/or quality as compared to a method using the same population of stem cells and/or progenitor cells without SH2B3 inhibition or disruption. Also provided herein are methods of use of the RBCs produced using the methods described herein.

Disclosed herein are methods for producing red blood cells (RBCs) from a population of stem cells and/or progenitor cells. In at least one of the stem cells or progenitor cells, SH2B3 protein activity is decreased, SH2B3 mRNA level is decreased, and/or SH2B3 protein level is decreased. The methods provided herein permit the production of RBCs with increased quantity and/or quality as compared to a method using the same population of stem cells and/or progenitor cells without SH2B3 inhibition or disruption. Also provided herein are methods of use of the RBCs produced using the methods described herein.

The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

The present invention features compositions and methods for editing deleterious mutations associated with hemoglobinopathies, such as sickle cell disease (SCD). In particular embodiments, the invention provides methods for correcting mutations in a beta globin polynucleotide using modified adenosine base editors termed “ABE8” having unprecedented levels (e.g., >60-70%) of efficiency.

The present invention relates to the in vitro production of erythrocytes/granulocytes and to the treatment of myelodysplastic syndrome using a method for inducing hemoblast differentiation. The present invention provides a media composition comprising gelsolin as an active ingredient for inducing the differentiation of hematopoietic precursor cells into erythrocytes/granulocytes, and a pharmaceutical composition comprising gelsolin as an active ingredient for treating myelodysplastic syndrome. Since the composition of the present invention improves the efficiency of differentiation of hematopoietic precursor cells into erythrocytes/granulocytes while maintaining a low rate of occurrence of cell dysplasia and having the effect of improving the enucleation rate and cell survivability, the present invention can be effectively used for producing erythrocytes/granulocytes in vitro and for treating myelodysplastic syndrome.

The present invention relates to the in vitro production of erythrocytes/granulocytes and to the treatment of myelodysplastic syndrome using a method for inducing hemoblast differentiation. The present invention provides a media composition comprising gelsolin as an active ingredient for inducing the differentiation of hematopoietic precursor cells into erythrocytes/granulocytes, and a pharmaceutical composition comprising gelsolin as an active ingredient for treating myelodysplastic syndrome. Since the composition of the present invention improves the efficiency of differentiation of hematopoietic precursor cells into erythrocytes/granulocytes while maintaining a low rate of occurrence of cell dysplasia and having the effect of improving the enucleation rate and cell survivability, the present invention can be effectively used for producing erythrocytes/granulocytes in vitro and for treating myelodysplastic syndrome.

Described herein are functionalizing nanocomplexes comprising one or more polyphenol molecules; and one or more biomolecules. Further described herein are functionalized cells comprising one or more of the nanocomplexes. In some embodiments, the biomolecules can be therapeutic agents and the functionalized cells can be administered to patients to provide improved delivery (e.g., dosing and specificity) of the therapeutic agent.

Described herein are functionalizing nanocomplexes comprising one or more polyphenol molecules; and one or more biomolecules. Further described herein are functionalized cells comprising one or more of the nanocomplexes. In some embodiments, the biomolecules can be therapeutic agents and the functionalized cells can be administered to patients to provide improved delivery (e.g., dosing and specificity) of the therapeutic agent.

The present invention provides biomarkers for sensitive, specific, accurate and quantitative diagnosis and assessment of chronic hypoxia. In particular, the present invention provides 2-hydroxyglutarate as a biomarker that is differentially produced in chronic hypoxia. Furthermore, embodiments of the invention are able to differentiate between chronic and acute hypoxia. Assays for levels of 2-hydroxyglutarate may be used alone or in conjunction with additional biomarkers of hypoxia to increase the precision of analysis. In particular embodiments of the invention, the level of 2-hydroxyglutarate and at least one second biomarker may be assayed to generate a hypoxic profile that can be compared to a reference or control profile, thereby diagnosing a subject as normoxic, chronically hypoxic, or acutely hypoxic.

The present invention provides biomarkers for sensitive, specific, accurate and quantitative diagnosis and assessment of chronic hypoxia. In particular, the present invention provides 2-hydroxyglutarate as a biomarker that is differentially produced in chronic hypoxia. Furthermore, embodiments of the invention are able to differentiate between chronic and acute hypoxia. Assays for levels of 2-hydroxyglutarate may be used alone or in conjunction with additional biomarkers of hypoxia to increase the precision of analysis. In particular embodiments of the invention, the level of 2-hydroxyglutarate and at least one second biomarker may be assayed to generate a hypoxic profile that can be compared to a reference or control profile, thereby diagnosing a subject as normoxic, chronically hypoxic, or acutely hypoxic.