The present disclosure provides CasX proteins, nucleic acids encoding the CasX proteins, and modified host cells comprising the CasX proteins and/or nucleic acids encoding same. CasX proteins are useful in a variety of applications, which are provided. The present disclosure provides CasX guide RNAs that bind to and provide sequence specificity to the CasX proteins, nucleic acids encoding the CasX guide RNAs, and modified host cells comprising the CasX guide RNAs and/or nucleic acids encoding same. CasX guide RNAs are useful in a variety of applications, which are provided. The present disclosure provides archaeal Cas9 polypeptides and nucleic acids encoding same, as well as their associated archaeal Cas9 guide RNAs and nucleic acids encoding same.

Provided is a peptide represented by the following formula (I):

TABLE-US-00001 R.sup.1-IWLTALX.sup.5FLGX.sup.6X.sup.1AAX.sup.7X.sup.2X.sup.3AX.sup.8QX.sup.4LSX.sup.9L-R.sup.2(I) wherein X.sup.1, X.sup.2, X.sup.3, X.sup.4, X.sup.5, X.sup.6, X.sup.7, X.sup.8, X.sup.9, R.sup.1, and R.sup.2 are as defined in the specification.

The invention provides compositions and methods for effective lysosomal targeting mediated by PCSK9. In particular, the compositions and methods provided by the invention may be used to treat lysosomal storage diseases such as Pompe Disease and Sanfilippo Syndrome Type B, and they may be used for targeting lysosomal enzymes to the various muscles of the human body.

Disclosed are exosomes that include a packaging protein and a cargo RNA in which the packaging protein binds specifically to the cargo RNA. The packaging protein is a fusion protein that includes an RNA-binding domain and an exosome-targeting domain. The cargo RNA includes an RNA-motif that the RNA-binding domain of the fusion protein binds specifically such that the cargo RNA is packaged in the lumen of the exosomes.

The present disclosure provides CasX proteins, nucleic acids encoding the CasX proteins, and modified host cells comprising the CasX proteins and/or nucleic acids encoding same. CasX proteins are useful in a variety of applications, which are provided. The present disclosure provides CasX guide RNAs that bind to and provide sequence specificity to the CasX proteins, nucleic acids encoding the CasX guide RNAs, and modified host cells comprising the CasX guide RNAs and/or nucleic acids encoding same. CasX guide RNAs are useful in a variety of applications, which are provided. The present disclosure provides archaeal Cas9 polypeptides and nucleic acids encoding same, as well as their associated archaeal Cas9 guide RNAs and nucleic acids encoding same.

The present invention relates to variants of acid-alpha glucosidase and uses thereof.

The present invention relates to variants of acid-alpha glucosidase and uses thereof.

Given developing resistance of tumor cells to current chemotherapeutic and targeted therapeutic agents, novel cancer therapies with enhanced potency and specificity are substantially required. Applicant has provided herein extracellular nanoparticle vesicles that redirect immune effector cells towards cancer cells for killing. Relative to conventional immunotherapeutic antibodies with defined orientation and geometry for their distinct antigen-binding arms, antibodies displayed on spherical exosomes can promote formation of immunological synapses as well as enhanced efficacy to activate immune cells.

The present invention relates to an engineered immune cell which comprises: (i) a target binding polypeptide comprising a target-binding domain and a first protein interaction domain, and (ii) a localising polypeptide comprising a second protein interaction domain, which binds to the first protein binding domain, and an intracellular retention signal. When the target binding polypeptide binds its target protein and also the localising polypeptide, expression of the target protein at the cell surface is reduced or eliminated because the target protein is retained in an intracellular compartment.

Provided are recombinant polypeptides that comprise a protein of interest, a protein localization tag, and a protease cleavage site disposed between the protein of interest and the protein localization tag. In certain embodiments, the recombinant polypeptides further comprise a protease, where the protease cleavage site is a cleavage site for the protease. Also provided are nucleic acids that encode the recombinant polypeptides, cells that comprise such nucleic acids, and compositions (e.g., pharmaceutical compositions) that comprise such cells. Methods of regulating cellular localization of a protein of interest, and methods of administering a regulatable cell-based therapy to an individual in need thereof, are also provided.