Provided is a genetically modified non-human mammal that comprises an anchor DNA sequence inserted at an endogenous locus of a secretory milk protein gene, wherein the anchor DNA sequence comprises a site-specific recombinase recognition site. Also provided is a genetically modified non-human mammal that comprises a transgene inserted at an endogenous locus of a secretory milk protein gene, wherein the transgene encodes a secretory protein and is operably linked to the endogenous promoter of said secretory milk protein gene, and wherein the transgene is flanked by a pair of site-specific recombinase resulting sites. The genetically modified non-human mammals provided can be used for producing the secreted recombinant protein encoded by the transgene from the milk produced by the genetically modified non-human mammals.

The present invention relates to a factor VII composition having a substantially homogeneous isoelectric point and to a method for formulating such a composition. The present invention also relates to the therapeutic use of a factor VII composition having a substantially homogeneous isoelectric point.

The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Igα and/or Igβ 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 Igα and/or Igβ sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Igα and/or Igβ results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

Deferred treatment of nerve injuries is provided. Accordingly, there is provided a method of deferred treatment of a nerve injury in a subject in need thereof, the method comprising implanting at least 1 week following onset or diagnosis of the nerve injury in the subject a composition comprising a hyaluronic acid, a laminin polypeptide and an antioxidant at or near the nerve injury of the subject.

Disclosed herein is a recombinant nucleic acid, comprising: a mitochondrial targeting sequence; a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein; and a 3′UTR nucleic acid sequence. Also disclosed is a pharmaceutical composition comprising the recombinant nucleic acid and a method of treating Leber's hereditary optic neuropathy (LHON) using the pharmaceutical composition.

The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Igα and/or Igβ 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 Igα and/or Igβ sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Igα and/or Igβ results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

Herein is reported a transgenic vector comprising a humanized light chain locus, wherein said humanized light chain locus comprises (a) a V gene segment derived from human light chain V segment IGKV1-39-01, (b) 3′ proximal to said light chain gene segment a promoter, and (c) 5′ proximal to said light chain gene segment at least a fragment of the human IGKJ4 J-element.

Disclosed herein is a recombinant nucleic acid, comprising: a mitochondrial targeting sequence; a mitochondrial protein coding sequence, wherein said mitochondrial protein coding sequence encodes a polypeptide comprising a mitochondrial protein; and a 3′UTR nucleic acid sequence. Also disclosed is a pharmaceutical composition comprising the recombinant nucleic acid and a method of treating Leber's hereditary optic neuropathy (LHON) using the pharmaceutical composition.

The present invention provides a genetic modification non-human organism in which an expression level of Cas9 is high and a plurality of different genes or a plurality of different locations in the same gene can be edited at the same time with high efficiency. The genetic modification non-human organism of the present invention includes a nuclear genome having at least 3 copies of genes that code for Cas9 (CRISPR-associated 9). Egg cells of the present invention are derived from the genetic modification non-human organism having the nuclear genome into which at least 3 copies of genes that code for the Cas9 are introduced. Fertilized eggs of the present invention are obtained by fertilizing the egg cells and sperm derived from the same species of the organism. A method for modifying target genes of the present invention includes a step of introducing a guide RNA into cells derived from the genetic modification non-human organism, the egg cells, or the fertilized eggs.

The present application provides genetically modified non-human animals and methods for producing heavy chain-only antibodies (HcAbs), wherein the genetically modified non-human animal comprises a germline genome comprising an engineered immunoglobulin heavy chain (IgH) allele at an endogenous IgH locus, wherein the engineered IgH allele lacks functional gene segments encoding CH1 domains of all endogenous IgG subclasses. In some embodiments, a genetically modified mouse is provided, comprising an engineered IgH allele that lacks a functional endogenous gene segment encoding Cγ3, Cγ1, Cγ2b and CH1 exon of Cγ2c. Further provided are HcAbs or derivatives thereof produced by the genetically modified non-human animals.