Methods for making hemoglobin based blood substitute preparations and hemoglobin based blood substitute preparations. The methods involve preparing a low purity erythrocyte protein fraction comprising hemoglobin protein and endogenous non-hemoglobin protein complement, and chemically modifying the proteins in the protein fraction to form a cross-linked hemoglobin containing blood substitute preparation. The low purity erythrocyte protein preparation can contain from at least about 0.2% (mole/mole) up to about 20% (mole/mole) endogenous non-hemoglobin protein complement. At least about 90% (mole/mole) of the hemoglobin proteins can be cross-linked, so that the average molecular mass of cross-linked proteins comprising hemoglobin protein molecules in the preparation is at least about 300 kDa. The preparations can be used to prepare finished blood substitute formulations for in-vivo and ex-vivo use.

Populations of cells enriched in fetal cells from a biological sample obtained from a pregnant subject are prepared using microbubbles, resulting in a sufficient number of fetal cells having a quality suitable for sequencing and providing non-invasive prenatal diagnosis of genetic disorders.

Provided herein are nucleic acid molecules that target the BCL11A enhancer functional regions, compositions comprising the nucleic acid molecules and methods for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels. In particular, the nucleic acid molecules target the +62, +58, and/or the +55 enhancer functional regions.

Methods for making hemoglobin based blood substitute preparations and hemoglobin based blood substitute preparations. The methods involve preparing a low purity erythrocyte protein fraction comprising hemoglobin protein and endogenous non-hemoglobin protein complement, and chemically modifying the proteins in the protein fraction to form a cross-linked hemoglobin containing blood substitute preparation. The low purity erythrocyte protein preparation can contain from at least about 0.2% (mole/mole) up to about 20% (mole/mole) endogenous non-hemoglobin protein complement. At least about 90% (mole/mole) of the hemoglobin proteins can be cross-linked, so that the average molecular mass of cross-linked proteins comprising hemoglobin protein molecules in the preparation is at least about 300 kDa. The preparations can be used to prepare finished blood substitute formulations for in-vivo and ex-vivo use.

The present invention relates to a fetal cell capture module, a microfluidic chip for fetal cell capture, and methods for using the same. The fetal cell capture module comprises a cell capture carrier and recognition molecule(s) for specific capture the cell(s). The recognition molecule is attached to the surface of the carrier via an organic conjugate L comprising disulfide bonds. The surface of the chip is modified with recognition molecules that specifically capture fetal cells via organic conjugates comprising disulfide bonds. The recognition molecule, after capturing the cell, achieves the release of the cell by chemically cleaving the disulfide bonds in the organic coupling conjugate. The present invention enables the capture of fetal cell(s) from whole blood without pre-treatment with a high capture rate, low cell loss, simple and accurate cell release operation, and the efficient and noninvasive release of fetal cells and whole genome analysis.

A method of making an erythroid cell comprising elevated levels of a target protein or polypeptide, the method comprising: a) provision of an erythroid progenitor which is able to express the target protein or polypeptide; b) expression of the target protein or polypeptide; and c) maturation of the erythroid progenitor into the erythroid cell; wherein during maturation of the erythroid progenitor into the erythroid cell, the target protein or polypeptide is configured and/or inhibited such that ubiquitination of the target protein or polypeptide is hindered or prevented. Erythroid cells, pharmaceutical compositions and methods of use related thereto, and a method of screening for proteins or polypeptides degraded by ubiquitination during maturation of an erythroid progenitor are also provided.

This application provides methods, compositions, and kits for use blood group determination and the preparation of improved red blood cell containing reagents for use in blood typing of blood prior to its use in transfusion medicine.

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.

A hydrogel capsule comprising a stem cell core that has been induced to differentiate into a hematopoietic lineage cell, and methods for the production of hematopoietic lineage cells from stem cells encapsulated in a hydrogel.

Methods for using cyclin-dependent kinase (CDK) inhibitors to enhance growth and self-renewal of progenitor cells, in vitro and in vivo.