The present invention is directed to a chimeric antigen receptor fusion protein comprising: (i) a single-chain variable fragment (scFv) comprising V.sub.H and V.sub.L, wherein scFv has an activity against a tumor antigen, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain; wherein the CAR further comprises a human transferrin fragment, which is an epitope for an antibody against human transferrin, at N-terminus or C-terminus to scFv, or between V.sub.H and V.sub.L. Preferred tumor antigens are CD19, CD22 and BCMA. The CD19-TF-CAR-T cells, CD22-TF-CAR-T cells, and BAMA-TF CAR-T cells secrete less cytokines, but they have the same efficacy against cancer target cells when comparing with same CAR without TF.

Disclosed herein are engineered nucleases that bind and cleave a recognition sequence within intron 1 of a transferrin gene, and methods of using such engineered nucleases to produce a genetically-modified eukaryotic cell comprising a modified transferrin gene. Further provided are pharmaceutical compositions and methods for treatment of a variety of conditions through expression of a polypeptide of interest encoded by an exogenous nucleic acid molecule inserted in intron 1 of a transferrin gene and expressed under the control of the endogenous transferrin promoter.

Disclosed herein are engineered nucleases that bind and cleave a recognition sequence within intron 1 of a transferrin gene, and methods of using such engineered nucleases to produce a genetically-modified eukaryotic cell comprising a modified transferrin gene. Further provided are pharmaceutical compositions and methods for treatment of a variety of conditions through expression of a polypeptide of interest encoded by an exogenous nucleic acid molecule inserted in intron 1 of a transferrin gene and expressed under the control of the endogenous transferrin promoter.

The present disclosure provides methods of modulating an immune response in an individual. The present disclosure provides methods of treatment. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) and an immune checkpoint inhibitor to an individual. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) to an individual who is undergoing treatment with immune checkpoint inhibitor.

The present disclosure provides methods of modulating an immune response in an individual. The present disclosure provides methods of treatment. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) and an immune checkpoint inhibitor to an individual. The present disclosure provides methods comprising administering a multimeric polypeptide (synTac) to an individual who is undergoing treatment with immune checkpoint inhibitor.

Provided are recombinant Factor VIII proteins, e.g., human Factor VIII proteins with heterologous moieties inserted into flexible permissive loops located in the Factor VIII A domains, while retaining the procoagulant activity of Factor VIII.

Provided are recombinant Factor VIII proteins, e.g., human Factor VIII proteins with heterologous moieties inserted into flexible permissive loops located in the Factor VIII A domains, while retaining the procoagulant activity of Factor VIII.

An engineered AAV capsid is provided, in which at least one protein on the capsid is modified to include a n-mer motif, which promotes transduction of the capsid into the central nervous system (CNS) through interaction with the Transferrin receptor. Further embodiments provide a vector system comprising one or more vectors encoding AAV capsids and a method of delivering cargo to the CNS. The method comprises administering, in vivo or in vitro, a AAV capsid according to embodiments described herein and the AVV capsid comprises one or more cargo molecules.

The present invention provides a derived peptide of a lactoferrin, a composition comprising the same and a use thereof for promoting and/or increasing lipid synthesis. The derived peptide of the lactoferrin comprises the amino acid sequence of SEQ ID NO: 01.

Provided is a method of activating gene expression using a protein having 90% or more sequence identity to SEQ ID NO:45. The protein activates the expression of a gene upon induction with a medium-chain or long-chain alkane or a medium-chain or long-chain fatty acid methyl ester. Also provided is a whole-cell catalytic system regulated by a medium-chain or long-chain alkane or a medium-chain or long-chain fatty acid methyl ester. The system includes a recombinant microbial cell expressing the protein and an alkane monooxygenase. Also provided is a method of preparing a medium-chain or long-chain alkane terminal oxidation product using the whole-cell catalytic system.