A non-human animal model for neurodegenerative and/or inflammatory diseases is provided, which non-human animal comprises a disruption in a C9ORF72 locus. In particular, non-human animals described herein comprise a deletion of an entire coding sequence of a C9ORF72 locus. Methods of identifying therapeutic candidates that may be used to prevent, delay or treat one or more neurodegenerative (e.g., amyotrophic lateral sclerosis (ALS, also referred to as Lou Gehrig's disease) and frontotemporal dementia (FTD)), autoimmune and/or inflammatory diseases (e.g., SLE, glomerulonephritis) are also provided.

The invention provides compositions and methods useful for the treatment and prevention of conditions associated with short telomere length.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use,

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A. In some embodiments, the present disclosure provides methods for dosing a hemophilia A patient with a polynucleotide, e.g., a codon-altered polynucleotide, encoding a Factor VIII polypeptide.

A highly glycosylated human blood-clotting factor VIII (FVIII) fusion protein, and a manufacturing method and application of same. The fusion protein comprises, from the N-terminus to the C-terminus, a human (FVIII), a flexible peptide connector, at least one rigid unit of a human chorionic gonadotropin β-subunit carboxyl terminal peptide, and a half-life extending portion (preferentially selected from a human IgG Fc variant). The fusion protein has a similar level of biological activity as a recombinant (FVIII) and an extended in vivo half-life, thereby improving pharmacokinetics and drug efficacy.

The invention relates to a new, spontaneous mouse lymphoma cell line displaying CD19, B220, MHC II, surface IgG2a/kappa chain and MAC-1, which is negative for CD5, animal models of B-cell lymphoma based on said cell line and methods for assessing lymphoma propagation and lymphoma expansion based on said cell line.

The invention relates generally to genetically modified non-human animals expressing human polypeptides and their methods of use.

The present disclosure relates to the use of RET, a transmembrane tyrosine kinase receptor, agonist molecules for Haematopoietic Stem Cell (HSC) expansion protocols and HSC transplantation therapy. RET signaling molecules are expressed by HSCs and Ret ablation leads to reduced HSC numbers. RET signals provide HSCs with critical Bcl2 and Bcl2l1 surviving cues, downstream of p38/MAP kinase and CREB activation. Accordingly, enforced expression of RET down-stream targets, Bcl2 or Bcl2l1, is sufficient to restore the activity of Ret null progenitors in vivo. Remarkably, activation of RET improves HSC survival or maintenance and in vivo transplantation efficiency, thus opening new horizons to the usage of RET agonist in HSC expansion and transplantation protocols. Additionally, the present disclosure describes a kit comprising RET agonist molecules, to be used in HSC expansion protocols and transplantation therapy.

The invention relates generally to a composition and method for increasing the frequency, amount, or presence of red blood cells in peripheral blood. In one embodiment, the invention comprises the inhibition of, or genetic modification of the genes encoding, one or more scavenger receptors. In one aspect, the invention relates to treatments of anemia.

The invention provides compositions and methods useful for the treatment and prevention of conditions associated with short telomere length.