The invention is in the field of molecular diagnosis of medical diseases and their treatment. More in particular, it provides methods and means for detecting hypertension, more in particular essential primary hypertension, even more in particular NOX5-dependent hypertension. The invention also provides methods for the treatment of hypertension, in particular essential primary hypertension, more in particular NOX5-dependent hypertension. The invention also provides theragnostics, wherein therapy is combined with diagnosis, more in particular wherein the level of NOX5 is determined in a sample from a subject and wherein the subject is treated with NOX5 inhibitors or compounds that decrease the levels of NOX5 if the NOX5 levels are above a certain threshold value. Further, the invention also provides theragnostics, wherein diagnosis is combined with therapy, more in particular wherein the (plasma) level of NOX5 is determined in a sample from a subject and wherein the subject is treated with NOX5 inhibitors or compounds that reverse the result of NOX5 activity in the subject, when the determined NOX5 level is exceeding a predetermined threshold level. Finally, the invention relates to an animal model suitable for developing diagnostic methods and therapeutic treatments for NOX5-dependent hypertension.

The present disclosure relates to genetically modified non-human animals that express a fusion protein including B2M and FcRn, and methods of use thereof. In some embodiments, the animals can have a B-NDG background. In some embodiments, the endogenous B2M gene is knocked out in the animals.

Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human V.sub.H gene segment, a plurality of human D.sub.H gene segments and a plurality of human J.sub.H gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.

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.

A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.

Provided are improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. Also provided are improved gene therapy methods for treating hematopoietic-related disorders. Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

The present disclosure provides multispecific antigen-binding molecules capable of binding to CD3 and CD137 (4-1BB) but not binding to CD3 and CD137 at the same time, and capable of binding to CLDN6. The multispecific antigen-binding molecules of the present disclosure exhibit enhanced T-cell dependent cytotoxicity activity in a CLDN6-dependent manner through binding to the CD3/CD37 and CLDN6. The present invention provides multi-specific antigen-binding molecules and pharmaceutical compositions thereof that can be used for targeting cells expressing CLDN6, for use in immunotherapy for treating various cancers, especially those associated with CLDN6 such as CLDN6-positive cancers.

Non-human animal cells and non-human animals comprising a humanized Asgr1 locus and methods of using such non-human animal cells and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized Asgr1 locus express a human ASGR1 protein or an Asgr1 protein, fragments of which are from human ASGR1. Methods are provided for using such non-human animals comprising a humanized Asgr1 locus to assess in vivo efficacy of human-ASGR1-mediated delivery of therapeutic molecules or therapeutic complexes to the liver and to assess the efficacy of therapeutic molecules or therapeutic complexes acting via human-ASGR1-mediated mechanisms.

The present disclosure relates to genetically modified non-human animals expressing human or chimeric (e.g., humanized) Thrombopoietin (THPO), and methods of use thereof.

The invention provides a genetically modified non-human animal that comprises in its genome unrearranged T cell receptor variable gene loci, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified non-human animal and methods of making the same. Various methods of using the genetically modified non-human animal are also provided.