The present invention provides proteins, nucleic acids, systems and methods for modulating RNA.

Methods, systems, compositions and strategies for the delivery of WW domain-containing fusion proteins into cells in vivo, ex vivo, or in vitro via ARMMs are provided. Methods, systems, compositions and strategies for the delivery of Cas9 proteins and/or Cas9 variants into cells in vivo, ex vivo, or in vitro via fusion to ARMM associated proteins (e.g., ARRDC1 or TSG101) are also provided.

Disclosed herein are chimeric proteins that include one or more double stranded nucleic acid binding domains (dsNABD) and one or more polyHis domains, and compositions that further include a therapeutic double stranded nucleic acid and a targeting ligand bound to the therapeutic double stranded nucleic acid, wherein the dsNABD of the chimeric protein is bound to the therapeutic double stranded nucleic acid, and uses of the compositions to treat disease.

The present invention pertains to extracellular vesicle (EV) therapeutics, wherein the EVs comprise nucleic acid (NA)-based therapeutics such as mRNAs, circular RNAs, miRNAs, shRNAs, and/or DNA molecules. The NA therapeutics are loaded into EVs using inventive protein and NA engineering strategies which stabilize the cargo NAs and enhance loading into EVs, thereby enhancing therapeutic activity of the cargo NA molecules half-life.

A polypeptide probe, including: from two to four G4-binding domains, and one or more linkers disposed between every two G4-binding domains. Each G4-binding domain includes a specific motif including a sequence of amino acids

TABLE-US-00001 (SEQ ID NO: 1) PGHLKGREIGMWY.

The present disclosure provides non-natural reverse transcriptases for conducting reverse transcription. The non-natural reverse transcriptases herein may have increased thermostability and can conduct reverse transcription more efficiently than natural reverse transcriptases.

Provided herein, in some aspects, are compositions and methods for artificially modulating alternative splicing, for example, inducing exon inclusion and/or exon exclusion events. In some embodiments, a catalytically inactive programmable nuclease, such as dCasRx, is fused to an RNA-binding protein (or fragment or isoform thereof) and, when guided to a target of interest by a specific guide RNA (gRNA), can regulate alternative splicing in eukaryotic cells.

Provided herein are CRISPR-based synthetic repression systems as well as methods and compositions using the synthetic repression systems to treat septicemia, an adverse immune response in a subject and Waldanstrom macroglobulinemia.

Materials and methods for using modified Cas9-APOBEC fusion polypeptides for targeted modification of specific DNA sequences are provided herein.

Provided are processes and materials for solving biological or structural information about proteins or other organic molecules. The processes capitalize on a rigid multimeric nanocage formed from self-assembling substructure proteins. The processes and materials allow for recognition and tight, optionally covalent, bonding of any protein molecule with a tag complementary to a capture sequence on the nanocage. The processes and materials may be used to obtain biological or structural information by cryo-electron microscopy and overcome prior limitations of target protein size or salt concentration.