The invention provides double knockout transgenic pigs (GT/CMAH-KO pigs) lacking expression of any functional ?GAL and CMAH. Double knockout GT/CMAH-KO transgenic organs, tissues and cells are also provided. Methods of making and using the GT/CMAH-KO pigs and tissue are also provided.

Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in combination with mitochondrial transit peptides in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been modified or edited.

The invention provides peptides derived from a ubiquitous protein, and nucleic acids encoding such peptides. The invention extends to various uses of these peptides and nucleic acids, for example, as antigens for use in vaccines per se and in the generation of antibodies for use in therapeutic drugs for the prevention, amelioration or treatment of infections caused by sepsis-inducing bacteria. The invention particularly benefits immunocompromised hosts such as neonates, babies, children, women of fertile age, pregnant women, foetuses, the elderly and diabetics.

Disclosed herein are methods of treating HIBM in a subject comprising identifying subject in need thereof; and administering to the subject a compound, or a pharmaceutically acceptable salt, ester, amide, glycol, peptidyl, or prodrug thereof, wherein the compound is a compound that is biosynthesized in a wild type individual along a biochemical pathway between glucose and sialic acid, inclusive. Also disclosed herein are vectors comprising a nucleic acid sequence that encodes a polypeptide having at least 80% sequence identity to the sequence set forth in SEQ ID NO:2, recombinant cells comprising these vectors, and recombinant animals comprising the cells. In addition, methods of identifying a compound having therapeutic effect for HIBM are disclosed.

The present invention relates to methods of treating diabetes in a human subject comprising the use of pancreatic islets or of embryonic pancreatic tissue of a transgenic animal, wherein said transgenic animal contains a polynucleotide sequence encoding a CTLA4 peptide-immunoglobulin fusion, preferably LEA29Y, and expresses said CTLA4 peptide-immunoglobulin fusion in a tissue-specific manner in pancreatic islets.

The presently subject matter provides novel human sequence antibodies against human CTLA-4 and methods of treating human diseases, infections and other conditions using these antibodies.

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.

The invention described herein provides high throughput methods and reagents for generating transgenic animals (e.g., non-human mammals) through introducing a CRISPR/Cas9 system comprising a Cas9 protein into gametes or preimplantation stage embryos (e.g., one-cell embryos or zygotes) via multiple cycles (e.g., 4-10 cycles) of electroporation, leading to genetically inheritable modification to the genome of the animal.

The present invention provides a delivery technique for delivering a gene modification tool capable of providing a high gene modification efficiency in cells. The composition according to the present invention is a composition for inducing gene modification at a target gene locus in a cell, the composition containing 1) a compound represented by formula (I) or a salt thereof; 2) a structural lipid; and 3) a guide RNA or a DNA including a sequence encoding the guide RNA, and/or an RNA-guided nuclease or a nucleic acid including a sequence encoding the RNA-guided nuclease. In formula (I), n represents an integer of 2 to 5, R represents a linear C.sub.1-5 alkyl group, a linear C.sub.7-11 alkenyl group, or a linear C.sub.11 alkadienyl group, and wavy lines each independently represent a cis-type bond or a trans-type bond. ##STR00001##

The present invention relates to transgenic ornamental fish, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing.