Engineered transversion base editors that enable expanded amino acid modifications and methods of using the same. Described herein, for example, are fusion proteins containing cytidine deaminases (e.g. human or rat APOBECs, pmCDA1 or AID) or adenosine deaminases (e.g. E. coli TadAs) or a combination thereof, catalytically impaired CRISPR-Cas proteins (e.g. Cas9, CasX or Cas12 nucleases), linkers, nuclear localization signals (NLSs) and a human or E. coli uracil-n-glycosylase (UNG) and/or REV1 protein that enable the CRISPR-guided programmable introduction of C-to-G and G-to-C transversions in DNA. The UNG may be fused to the deaminase-Cas fusion or not, in which case endogenous UNG may be recruited using molecular machinery that is integrated into the deaminase-Cas fusion architecture, e.g. using peptide or RNA aptamers or scFVs, sdABs or Fabs.

Compositions and methods are provided for metabolically degrading ADMA. In one embodiment a device is provided for reducing a patients ADMA levels in their blood wherein the device comprises a biologically active dimethylarginine dimethylaminohydrolase (DDAH) polypeptide covalently linked to a solid support. In one embodiment a method for reducing ADMA levels in a patients blood comprises the step of contacting the patients blood or a blood fraction with an immobilized biologically active DDAH polypeptide, wherein contact of the patients blood with said DDAH polypeptide results in degradation of ADMA present in the patients blood.

Provided herein is a composition comprising a fusion protein or a fragment or a variant thereof comprising an anti-PD1 antibody or a fragment/variant thereof and a TGF-β trap. Provided herein is a composition comprising a fusion protein or a fragment thereof or a variant thereof comprising an anti-PD1 antibody or a fragment/variant thereof and a ADA2 polypeptide. Also provided herein are methods of using the composition in treating cancer.

A recombinant lentiviral vector containing a gene encoding a TRAIL protein and a CD protein; and a cell that is transfected with the lentivirus produced by using the vector. A host cell transfected with the recombinant lentivirus maintains a high cell proliferation rate and overexpresses a TRAIL protein and a CD protein. Thus, a mesenchymal stem cell transfected with the lentivirus may be usefully employed as a cell therapeutic agent.

A recombinant lentiviral vector containing a gene encoding a TRAIL protein and a CD protein; and a cell that is transfected with the lentivirus produced by using the vector. A host cell transfected with the recombinant lentivirus maintains a high cell proliferation rate and overexpresses a TRAIL protein and a CD protein. Thus, a mesenchymal stem cell transfected with the lentivirus may be usefully employed as a cell therapeutic agent.

An isolated antigen-binding protein characterised in that it is capable of binding specifically to human Arginase II (ARG2) and inhibiting the enzyme activity of human ARG2.

An isolated antigen-binding protein characterised in that it is capable of binding specifically to human Arginase II (ARG2) and inhibiting the enzyme activity of human ARG2.

Provided herein are compositions and methods of using base editors comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain in conjunction with a guide polynucleotide. Also provided herein are base editor systems for editing nucleobases of target nucleotide sequences.

Provided herein are compositions and methods of using base editors comprising a polynucleotide programmable nucleotide binding domain and a nucleobase editing domain in conjunction with a guide polynucleotide. Also provided herein are base editor systems for editing nucleobases of target nucleotide sequences.

Described herein are production cells, and methods for identifying, selecting, or culturing production cells comprising tyrosine auxotrophy selection marker system, based on a combination of sequence encoding a phenylalanine hydroxylase (PAH) which lacks a functional N-terminal regulatory domain, and a sequence encoding a GTP cyclohydrolase 1 (GCH1). Also described are methods of making a production cell and making a product with said production cell.