The invention discloses methods for the generation of chimaeric human—non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

Provided herein are methods of treating a subject with Cockayne Syndrome (CS) or a predisposition thereto. Also provided are methods of treating a subject with one or more mutations in an ERCC5 gene, an ERCC8 gene, an ERCC6 gene, or a combination thereof, methods of delaying the onset of Cockayne Syndrome (CS), or a symptom thereof, in a subject with one or more mutations in an ERCC5 gene, an ERCC8 gene, an ERCC6 gene, or a combination thereof, and methods of slowing, halting or reversing progression of Cockayne Syndrome (CS) in a subject. In exemplary embodiments, the method comprises administering to the subject a replication-incompetent Adeno-associated Vims (riAAV) comprising a nucleotide sequence encoding a Xeroderma Pigmentosum group G (XPG) protein, a Cockayne Syndrome type A (CSA) protein, or a Cockayne Syndrome type B (CSB) protein in an effective amount. Provided herein are related Adeno-associated Virus and cells comprising the same.

Disclosed are methods for treating or limiting development of diabetes, by transplanting into the eye of a subject with diabetes or at risk of diabetes an amount effective to treat or limit development of diabetes of insulin-producing cells engineered to reduce expression of a β3 subunit of Cav (Cavβ3).

As disclosed herein, β-arrestin1 and β-arrestin2 levels are highly elevated in brains of FTLD-tau patients suggesting that both β-arrestin1 and β-arrestin2 are elevated in the brains of patients with AD and FLTD. The current work also shows that when β-arrestin2 is overexpressed, tau levels become elevated. The data indicate that β-arrestin2 reduces tau clearance by impairing p62-mediated autophagy, a role carried out by the oligomerized form of β-arrestin2. Therefore, disclosed herein are β-arrestin oligomerization inhibitors that can be used to prevent β-arrestin oligomerization and therefore the accumulation of tau in cells, i.e. tauopathy. Also disclosed are methods of treating a tauopathy in a subject that involve administering to the subject a therapeutically effective amount of a β-arrestin oligomerization inhibitor disclosed herein.

The present disclosure relates to the genetically modified non-human animals that express a human or chimeric TIGIT (e.g., humanized TIGIT), and methods of use thereof.

A method of producing a conditional knockout animal, and techniques related thereto, e.g., a method of efficiently producing a floxed animal, are provided. By introducing recombinase recognition sequences such as loxP into both ends of a target region on a chromosome at different timings, an animal having the pair of recombinase recognition sequences on the chromosome, such as a floxed animal, is produced.

A primatized rodent or swine, and methods of making and using the primatized rodent or swine, are provided.

Disclosed herein are rodents (such as mice and rats) genetically modified at an endogenous Scn9a locus to comprise an exogenous Scn nucleotide sequence such as the coding sequence of a human SCN2A gene. Also disclosed are methods and compositions useful for making such rodents, and methods of using such rodents for generating anti-NaV1.7 antibodies.

A non-human mammalian model for human diseases or disorders comprising a non-human neutrophil depleted mammalian host engrafted with a human skin equivalent (huSE) and human immune cells.

Provided is use of thiamine pyrophosphokinase TPK as a target in the treatment of Alzheimer's disease; and AD symptoms due to the inhibited TPK can be prevented by promoting the kinase activity and/or expression level of TPK protein in brain with TPK as a target.