The present disclosure relates to methods of screening salmonids for increased resistance to viral infection, such as infectious pancreatic necrosis virus (IP-NV) infection. The present disclosure also relates to fish which have been genetic modified to have increased resistance to viral/IPNV infection. The present disclosure further relates to the use of these fish, which have been identified. or genetically modified to have increased genetic resistance. in aquaculture breeding programs and/or production. The present disclosure further relates to the use of small molecules which target NAE1 and their use in therapy or prevention of viral/IPNV infection.

The disclosure relates to a method of introducing mRNA encoding Cas9 protein (Cas9 mRNA) into a mammalian embryo, comprising the steps of; (a) placing a mixture of the mammalian embryo and a solution comprising Cas9 mRNA in the gap between a pair of electrodes, and (b) applying a voltage to the electrodes for a voltage application duration, wherein the voltage and the voltage application duration achieve the efficiency of mRNA introduction (R) higher than the minimum required efficiency of mRNA introduction (R.sub.min) that is calculated on the basis of the concentration of Cas9 mRNA (ng/l).

The present disclosure generally relates to compositions and methods for improving the efficiency of homologous recombination. In particular, the disclosure relates to reagents and the use of such reagents.

The present disclosure provides a novel gene drive methodology that can be used to spread engineered traits into a targeted population. More specifically, the present disclosure provides a method of using a transgenic line containing a modified Cas9, e.g., nickase Cas9, that introduces single-strand breaks/nicks, instead of double-stranded DNA cuts, to promote super-Mendelian inheritance of an engineered gene drive allele. The present disclosure further provides a Cx.quin. Cas9 (e.g., nickase Cas9) line and a Cx.quin. gene-drive line for suppression populations.

Genetically modified non-human animals comprising a human or humanized interleukin-7 (IL-7) gene. Cells, embryos, and non-human animals comprising a human or humanized IL-7 gene. Rodents that express human or humanized IL-7 protein. Genetically modified mice that comprise a human or humanized IL-7-encoding gene in their germline, wherein the human or humanized IL-7-encoding gene is under control of endogenous mouse IL-7 regulatory sequences.

Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.

Genetically modified non-human animals comprising a human or humanized interleukin-7 (IL-7) gene. Cells, embryos, and non-human animals comprising a human or humanized IL-7 gene. Rodents that express human or humanized IL-7 protein. Genetically modified mice that comprise a human or humanized IL-7-encoding gene in their germline, wherein the human or humanized IL-7-encoding gene is under control of endogenous mouse IL-7 regulatory sequences.

Disclosed are gene edited ungulate animals and methods of editing genes that control various ungulate traits. Such methods include CRISPR, zinc fingers, or TALENS. Exemplary traits for editing include polled, sterility or fertility, milk production, growth (which increases meat production), fat production, conception rates, stillborn rates, calving ease, or content of produced milk such as the amount of protein or the amount of fat. Other traits include backfat thickness, intramuscular fat, ultrasound loin muscle area, loin muscle area and intramuscular fat content, chest circumference, withers height, body length, hip height, rump length, and heart girth. Other exemplary native traits include, but are not limited to, high altitude adaptation and response to hypoxia, cold acclimation, body size and stature, resistance to disease and bacterial infection, reproduction, milk yield and components, and feed efficiency.

Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.