This invention is directed to a vector which comprises a promoter operably linked to a nucleic acid sequence encoding the human C1 esterase inhibitor or Factor XII. The invention is also directed to a composition comprising the vector and a method of using the vector to treat or prevent hereditary angioedema.

Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

A polynucleotide that modulates transcription from a plurality of genomic targets can include, generally, a polynucleotide encoding a gRNA array and a polynucleotide sequence encoding a nuclease-deficient Cas9 polypeptide. The polynucleotide encoding a gRNA array generally includes polynucleotides encoding at least two gRNAs operably linked to an inducible regulatory sequence.

The invention provides methods of treating schizophrenia in a subject, including for example, administering to the subject an agent that inhibits expression or activity of a C4A polynucleotide or polypeptide. The invention also provides methods of identifying a subject having or at risk of developing schizophrenia involving measuring or detecting an alteration in the level, copy number, and/or sequence of complement component C4A or complement component C4B relative to a reference.

The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Ig and/or Ig sequences. Of particular interest are animals with transgenic heavy and light chain immunoglobulin loci capable of producing a diversified human(ized) antibody repertoire that have their endogenous production of Ig and/or endogenous Ig and/or Ig sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Ig and/or Ig results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

The present invention relates to a vector comprising a nucleic acid sequence that encodes the APP protein and/or the PS1 protein or variants thereof. The invention also relates to a method for inducing the Alzheimer's disease in an animal using the vector of the invention and to animal model having the Alzheimer's disease obtained by said method.

Provided herein are compositions and methods relating to cell-penetrating conjugates for the delivery of therapeutic polypeptides or polynucleotides to cells or tissues of the body. The delivery conjugate comprises a cell-penetrating peptide and a nuclear localization signal sequence plus an effector moiety (such as a polypeptide or polynucleotide) as the payload, optionally further including an epitope tag as well as a solubility peptide and a configurating peptide. The delivery conjugate can also include a component capable of specifically directing the conjugate to a target cell or tissue, making the conjugate effective for treating diseases in the target tissue.

In some aspects, the present invention provides chimeric transferrin receptor (TfR) polynucleotides and polypeptides. In other aspects, this invention provides chimeric TfR transgenic animal models and methods of using the animal models to identify therapeutics that can cross the blood-brain barrier.

The present invention concerns methods and means to produce humanized antibodies from transgenic non-human animals. The invention specifically relates to novel immunoglobulin heavy and light chain constructs, recombination and transgenic vectors useful in making transgenic non-human animals expressing humanized antibodies, transgenic animals, and humanized immunoglobulin preparations.

Described herein are anchor-modified immunoglobulin polypeptides, wherein the anchor moors the immunoglobulin polypeptide to a receptor of interest. The anchor-modified immunoglobulin polypeptides are generally characterized at the N-terminus with an anchor, e.g., the receptor binding portion of a ligand that binds a receptor. Non-human animals genetically modified with recombinant immunoglobulin segments that encode the anchor-modified immunoglobulin polypeptides are capable of making the anchor-modified immunoglobulin polypeptides. Such non-human animals also provided, along with methods and compositions for making and using the non-human animals. Methods for producing anchor-modified immunoglobulins from non-human animals are also provided, as well as anchor-modified immunoglobulins generated therefrom.