Abstract: Recombinant adenovirus genomes that include a heterologous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. The recombinant adenovirus genomes and recombinant adenoviruses produced by the disclosed genomes can be used, for example, in high-throughput assays to measure virus replication kinetics. Methods for measuring replication kinetics of a recombinant adenovirus are also described.

Abstract: Recombinant herpes simplex virus (HSV)-1 capable of selectively replicating in alternative lengthening of telomeres (ALT)-dependent tumor cells are described. The recombinant HSV-1 are ICP0-deficient, such as by complete deletion of the ICP0 gene, or mutation of the ICP0 gene sufficient to diminish or eliminate E3 ubiquitin ligase activity of ICP0. In some cases, the recombinant HSV-1 further include additional gene deletions or mutations, such as those that render the virus glycoprotein C (gC) deficient, or include a heterologous gene, such as a gene encoding an immunostimulatory molecule. Methods of treating ALT-dependent cancer, and methods of selectively killing ALT-dependent tumor cells are also described.

Abstract: Recombinant adenovirus genomes that include an exogenous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. Optimal placement of the exogenous genes for minimal impact on viral kinetics is further disclosed. Therapeutic applications of the recombinant adenoviruses are also described.

Abstract: Methods are provided for identifying Alzheimer's disease cells or subjects, based on the methylation status of multiple methylation markers in genomic DNA. Also provided are methods for identifying therapeutic agents for treating Alzheimer's disease by monitoring changes in the methylation status of multiple methylation markers.

Abstract: Provided herein are CRISPR/Cas methods and compositions for targeting RNA molecules, which can be used to detect, edit, or modify a target RNA.

Abstract: The invention features compositions and methods treating or preventing for age-related insulin resistance, type 2 diabetes and related disorders. The method involves depleting fTreg cells with an anti-ST2 antibody to decrease age-related fTreg accumulation and restore insulin sensitivity, thereby treating age-related insulin resistance, type 2 diabetes and related disorders.

Abstract: Methods of lowering blood glucose and treating Type 2 diabetes in a subject by increasing expression or activity of phosphodiesterase 4D isoform 3 (PDE4D3) in adipocytes of the subject are described. In some instances, expression of PDE4D3 in adipocytes is increased by administering a vector that expresses PDE4D3 specifically in adipocytes, or via gene editing by introduction of a PDE4D3-encoding nucleic acid into adipocytes. Use of small molecule activators of PDE4D3 that are targeted to adipocytes is also described.

Abstract: The present disclosure provides compositions and methods for regulating ethylene signaling in a plant or a plant tissue culture. The present disclosure also provides compositions and methods for modulating gravitropic set-point angle in plant roots via regulation of ethylene signaling. The present disclosure further provides small molecules that regulate ethylene signaling.

Abstract: Disclosed herein are homology-independent targeted integration methods of integrating an exogenous DNA sequence into a genome of a cell and compositions for such methods. Methods herein comprise contacting the cell with a composition comprising a targeting construct comprising the exogenous DNA sequence and a targeting sequence, a complementary strand oligonucleotide homologous to the targeting sequence, and a nuclease, thereby altering the genome of the cell.

Abstract: Compositions and methods for retargeting adenovirus to a cell using chemical dimers are described. In particular, a recombinant adenovirus comprising a nucleic acid comprising a capsid-dimerizing agent binder conjugate and a ligand-dimerizing agent binder conjugate is provided.

Abstract: Provided herein are compositions and systems for reconstitution of RNA molecules, including methods for using these molecules. For example, such molecules can be used to deliver a protein coding sequence over two or more viral vectors (such as AAVs), resulting in reconstitution of the full-length protein in a cell. Such methods can be used to deliver a protein involved in editing a nucleic acid molecule, for example to treat a genetic disease or cancer.

Abstract: Provided herein are multiplex crRNAs and multiplex sgRNAs, as well as RNA molecules thereof. Also provided are compositions and kits including the multiplex crRNAs and sgRNAs, which can be used in a multiplex targeted gene activation (mTGA) system. Also provided are methods that include administering a therapeutically effective amount of the mTGA system to a subject. In some examples, the method treats a disease associated with reduced or no expression of a gene, such as type I diabetes, Duchenne muscular dystrophy, a liver disease, or acute kidney disease.

Abstract: Synthetic adenoviruses with liver detargeting mutations and expressing an adenovirus type 34 (Ad34) fiber protein, or a chimeric fiber protein with an Ad34 knob domain, are described. The synthetic adenoviruses traffic to sites of tumors. Use of the synthetic adenoviruses for delivering diagnostic or therapeutic transgenes to tumors are also described.

Abstract: The invention generally features compositions comprising induced pluripotent stem cell progenitors (also termed reprogramming progenitor cells) and methods of isolating such cells. The invention also provides compositions comprising induced pluripotent stem cells (iPSCs) derived from such progenitor cells. Induced pluripotent stem cell progenitors generate iPSCs at high efficiency.

Abstract: Methods of modulating regulatory T (Treg) suppressor activity are provided. Also provided are methods of treating autoimmune diseases and methods of treating cancer. The methods include increasing or reducing the expression or activity of bromodomain-containing 9 (Brd9), bromodomain-containing 7 (Brd7), and/or polybromo 1 (Pbrm1) in a Treg cell or in a subject.

Abstract: Provided herein are CRISPR/Cas methods and compositions for targeting RNA molecules, which can be used to detect, edit, or modify a target RNA.

Abstract: Disclosed herein are homology-independent targeted integration methods of integrating an exogenous DNA sequence into a genome of a non-dividing cell and compositions for such methods. Methods herein comprise contacting the non-dividing cell with a composition comprising a targeting construct comprising the exogenous DNA sequence and a targeting sequence, a complementary strand oligonucleotide homologous to the targeting sequence, and a nuclease, thereby altering the genome of the non-dividing cell.

Abstract: The invention features pancreatic islet and pancreatic organoids, and cell cultures and methods that are useful for the rapid and reliable generation of pancreatic islet and pancreatic islet organoids. The invention also features methods of treating pancreatic diseases and methods of identifying agents that are useful for treatment of pancreatic diseases, such as type 2 diabetes and pancreatic cancer, using the pancreatic islet and pancreatic organoids of the invention.

Abstract: The invention provides compositions featuring TRP-4 polypeptides and polynucleotides, methods for expressing such polypeptides and polynucleotides in a cell type of interest, and methods for inducing the activation of the TRP-4 polypeptide in neurons and other cell types using ultrasound.

Abstract: The invention provides compositions featuring TRP-4 polypeptides and polynucleotides, methods for expressing such polypeptides and polynucleotides in a cell type of interest, and methods for inducing the activation of the TRP-4 polypeptide in neurons and other cell types using ultrasound.