An object of the present invention is to provide a method of conveniently producing a genetically modified non-human mammal with high efficiency using a CRISPR-Cas9 system and particularly a production method whereby gene knock-in can be achieved with high efficiency regardless of the gene size. The method of producing a genetically modified non-human mammal comprises introducing a Cas9 protein, a crRNA fragment comprising a nucleotide sequence complementary to a target DNA region, and a tracrRNA fragment into a non-human mammalian oocyte to genetically modify the target DNA.

Compositions and methods are provided for the inhibition, treatment and/or prevention of Huntington's disease and related disorders.

The present invention provides for a double stranded RNA comprising a first RNA sequence and a second RNA sequence wherein the first and second RNA sequence are substantially complementary, wherein the first RNA sequence has a sequence length of at least 19 nucleotides and is substantially complementary to SEQ ID NO. 1. Said double stranded RNA is for use in inducing RNAi against Huntingtin exon 1 sequences. The double stranded RNA of to the invention was capable of reducing neuronal cell death and huntingtin aggregates in an animal model.

A nucleic acid including a sequence encoding a single guide RNA (sgRNA) of a CRISPR/Cas system is disclosed, wherein the sgRNA sequence is interrupted by a guide disruption sequence flanked by a first pair of recombinase recognition sites, and wherein the sgRNA sequence further includes a second pair of recombinase recognition sites that has a different recombinase recognition sequence than the first pair of recombinase recognition sites, wherein the guide disruption sequence is not flanked by the second pair of recombinase recognition sites and wherein the sequences flanked by the first and second recombinase recognition sites overlap; methods of using such a sgRNA, transgenic cells and kits.

Disclosed herein are cells including pluripotent stem cells that conditionally express an immunosuppressive factor and related methods of their use and generation. In some embodiments, the cells disclosed do not express MHC I and MHC II human leukocyte antigens, and in some cases, also do not express one or more TCR complexes. In some embodiments, hypoimmunogenicity of the cells is controlled by activation of a controllable expression system upon contacting the cells with a specific factor or agent.

The present disclosure provides a transposon system comprising: i) a nucleotide sequence encoding polypeptides that form a CRISPR-associated transposase complex; ii) a nucleotide sequence encoding a guide RNA; and iii) a transposon, or an insertion site for a transposon, flanked by CAST complex recognition sites. The present disclosure provides a prokaryotic cell comprising a subject transposon system. The transposon system is useful for editing the genome of a target prokaryotic cell. The present disclosure provides methods for editing the genome of a target prokaryotic cell. The present disclosure further provides systems and methods for identifying, within a heterogeneous population of prokaryotic cells, prokaryotic species that are susceptible to genetic modification and gene editing.

In aspects, the present disclosure provides a method of treating or preventing a uterine fibroid in a female mammal, the method comprising, consisting essentially of, or consisting of administering to the female mammal an effective amount of an agent that modulates an N6-methyladenosine (m6A) regulator.

The present disclosure relates to recombinant viral vectors for the treatment and prevention of cancer. Oncolytic viral vectors incorporate one or more of the following features: viral replication restriction by insertion of tumor-suppressive microRNA (miRNA) target sequences into the viral genome; disruption of oncogenic miRNA function; cancer microenvironment remodeling; and cancer cell targeting by incorporation of protease-activated antibodies into the viral particle.

This invention generally relates to a composition and its method of use for inducing adult stem cell (ASC) expansion and/or derivation in vitro, using miR-302-like pre-miRNAs, shRNAs and/or siRNAs, all of which contain a shared sequence of 5′-UAAGUGCUUC CAUGUUU-3′ (SEQ ID NO: 7) in the 5′-end, and further in conjunction with the use of some wound-healing-related defined factors, including but not limited to basic fibroblast growth factor (bFGF)/fibroblast growth factor 2 (FGF-2), leukemia inhibitory factor (LIF), insulin-like growth factor (IGF), Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF), tumor necrosis factor (TNF), stem cell factor (SCF), homeobox proteins (HOX), Notch, GSK, Wnt/beta-Catenin signals, interleukins, and/or bone morphogenetic proteins (BMPs). The principle of the present invention is related to a novel mechanism of inducible symmetric ASC division recently found in a skin wound healing model in vivo. The resulting amplified ASCs are useful for treating a variety of human aging- and cell dysfunction-associated disorders, including but not limited to Alzheimer's disease, Parkinson's disease, motor neuron disease, stroke, diabetes, osteoporosis, myocardial infraction, hemophilia, anemia, AIDS, leukemia, lymphoma and many kinds of cancers as well as aging.

The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present invention generally relates to an immune cell comprising a genetically engineered antigen receptor that specifically binds to a target antigen and a genetic disruption agent that reduces or is capable of reducing the expression in the immune cell of a gene that weakens the function of the immune cell.