The present invention relates to processes and systems for preparing nanoparticles, cellular or viral membranes and/or cellular or viral membrane coated nanoparticles using or comprising, inter alia, a multi-inlet vortexing reactor, tangential flow filtration (TFF) and/or a high shear fluid processor such as a microfluidizer (or a microfluidizer processor). The present invention also relates to the nanoparticles, cellular or viral membranes and/or cellular or viral membrane coated nanoparticles prepared by the present processes and systems, and the uses and/or applications of the nanoparticles, cellular or viral membranes and/or cellular or viral membrane coated nanoparticles.

This disclosure provides methods of making a megakaryocyte-erythroid progenitor cell (MEP), comprising differentiating a MEP precursor cell into a MEP in culture in the presence of an aryl hydrocarbon receptor (AhR) modulator. In some embodiments the AhR modulator is an AhR antagonist. In some embodiments the AhR modulator is an AhR agonist. In some embodiments the methods comprise culturing MEP precursor cells in the presence of an AHR antagonist and then culturing MEP precursor cells in the presence of an AHR agonist. In some embodiments the stem cell is a pluripotent stem cell. In some embodiments the MEP co-expresses CD41 and CD235. In some embodiments the number of MEPs produced in the culture increases exponentially. Methods of making a red blood cell (RBC) by culturing a MEP in the presence of an AhR modulator are also provided. Methods of making a megakaryocyte and/or a platelet, comprising culturing a MEP in the presence of an AhR modulator are also provided. In some embodiments the AhR modulator is an AhR antagonist. This disclosure also provides compositions comprising at least 1 million MEPs per ml and compositions in which at least 50% of the cells are MEPs, among other things.

The present disclosure provides polynucleotide cassettes, expression vectors and methods for the expression of a gene in mammalian cells to provide gene therapy for pyruvate kinase deficiency.

Compositions, methods and systems for the treatment of a protein aggregation disease including, but not limited to Alzheimer's disease (AD), Parkinson's disease (PD), Dementia with Lewy Bodies (DLB), Huntington's disease (HD), Amylotrophic lateral sclerosis (ALS, which results from degeneration of the upper and lower motor neurones and affects the voluntary muscle system), Progressive Supranuclear Palsy (PSP), Type 2 Diabetes and Multiple systems atrophy (MSA).

The invention relates to a method for long-term ex vivo maintenance or expansion of one or more of a human erythroblast, a human megakaryocyte-erythroid progenitor, or a human common myeloid progenitor, comprising the step of: culturing cells comprising one or more of those cells in a culture medium comprising one or more selected from a tankyrase inhibitor, a growth factor, a B-Raf kinase inhibitor and a GSK-3 inhibitor.

Blood and platelet storage and rejuvenating compositions that include triciribine, triciribine metabolites, triciribine analogs, and mixtures of the same are disclosed. Such compositions can be useful in methods for treating (e.g., storing and rejuvenating) red blood cells and platelets.

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.

Disclosed herein are potency assays for a gene therapy treatment for β-thalassemia. Also disclosed herein are methods for measuring relative potency of a drug product.

Disclosed herein are potency assays for a gene therapy treatment for sickle cell disease. Also disclosed herein are methods for measuring relative potency of a drug product used for the treatment of sickle cell disease.

An erythrocyte differentiation monitoring apparatus includes a laser light source that radiates a pulsed laser beam in a hemoglobin absorption wavelength range onto a cell within a culture container, a probe that receives a photoacoustic wave emitted from the cell within the culture container as a result of the cell being irradiated with the pulsed laser beam emitted from the laser light source, and a processor that evaluates the progress of differentiation of the cell into an erythrocyte based on the intensity of the photoacoustic wave received by the probe.