Provided herein are systems and methods for Inducible and conditional CRISPR/Cas9 and RNAi. From animal model creation and the efficiency of CRISPR-based targeting, the present invention comprises developing RNAi models that enable inducible and reversible gene silencing to simulate new therapeutic regimes.

The present invention relates to animal models that expresses SR-BICT knockin. The present invention further includes animal models that express SR-BICT and also have reduced expression or activity of ApoE and/or LDLR, wherein the latter can be accomplished by use of a compound or genetic manipulation of the gene. The present invention relates to mouse models crossed with SR-BICT knockin mice. Specifically, the present invention relates to SR-BICT knockin mice crossed with apolipoprotein E (ApoE) knockout mice (SR-BICT/apoE KO), a hypoE mouse (also referred to as ApoeR61.sup.h/h which expresses an impaired ApoE protein (SR-BICT/ApoeR61.sup.h/h)), or a LDLR knockout mouse (SR-BICT/LDLR KO). Screening methods and compounds using these mouse models are also encompassed.

The invention in some aspects relates to isolated nucleic acids, compositions, and kits useful for identifying adeno-associated viruses in cells. In some aspects, the invention provides kits and methods for producing somatic transgenic animal models using recombinant AAV (rAAV) to an animal having at least one transgene that expresses a small interfering nucleic acid or at least one binding site for a miRNA.

According to the embodiments described herein, a series of biological materials for treatment/therapy of DMD and/or BMD through the recovery of sarcolemmal nNOS is provided. The biological material comprises the complete dystrophin repeats R16 and R17 or certain domains, sections, or fragments of the dystrophin repeats R16 and R17. In some aspects, such domains, sections, or fragments may be selected from sequence motifs including dystrophin R17 1 helix, 2 and 3 helices of both R16 and R17, or a combination thereof.

Provided is an improved design of shRNA based on structural mimics of miR-451 precursors. These miR-451 shRNA mimics are channeled through a novel small RNA biogenesis pathway, require AGO2 catalysis and are processed by Drosha but are independent of DICER processing. This miRNA pathway feeds active elements only into Agog because of its unique catalytic activity. These data demonstrate that this newly identified small RNA biogenesis pathway can be exploited in vivo to produce active molecules.

Provided herein is technology relating to molecular biological manipulation of genes and genomes and particularly, but not exclusively, to CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) methods, compositions, systems, and kits for improved genetic editing.

The invention in some aspects relates to isolated nucleic acids, compositions, and kits useful for identifying adeno-associated viruses in cells. In some aspects, the invention provides kits and methods for producing somatic transgenic animal models using recombinant AAV (rAAV) to an animal having at least one transgene that expresses a small interfering nucleic acid or at least one binding site for a miRNA.

Aspects of the disclosure include devices, systems and methods for optogenetic modulation of action potentials in target cells. The subject devices include light-generating devices, control devices, and delivery devices for delivering vectors to target cells. The subject systems include light-activated proteins, response proteins, nucleic acids comprising nucleotide sequences encoding these proteins, as well as expression systems that facilitate expression of these proteins in target cells. Also provided are methods of using the subject devices and systems to optogenetically inhibit and intercept action potentials in target cells, e.g., to treat a neurological or psychiatric condition in a human or non-human animal subject.

Aspects of the invention described herein relate to synthetic, modified RNAs and their use in vivo to modulate gene expression. Aspects of the invention further relate to the use of these synthetic, modified RNAs in myocytes, cardiomyoctes, and tumors.

Methods for the production of reproductively sterile fish and aquatic animals for aquaculture, the aquarium trade, and control of invasive species are described. The methods include disruption of gonadal development through the administration of compounds that lead to the failure of fertile gonadal development. Compounds may be delivered to the eggs prior to fertilization or water activation or post fertilization and water activation by contacting unfertilized or pre-water-activated fertilized eggs or fertilized eggs in an immersion medium including the compound of interest. Compounds may be conjugated with a molecular transporter compound effective for chorionic transport of the conjugate. The compounds may be antisense Morpholino oligomers that are capable of effectively suppressing the expression of the dead end gene or other essential genes for germ cell development in fish and other egg-producing aquatic animals.