The present disclosure generally relates to therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells may be generated in vitro/ex vivo as well as in vitro by delivering nucleic acid encoding an antigen receptor for genetic modification to cells using particles comprising the nucleic acid and a targeting molecule for targeting the immune effector cells, wherein the targeting molecule is a designed ankyrin repeat protein (DARPin). In particular, DARPins are described herein which are high-affinity binders for CDS binding to the CDS receptor on human and non-human primate (NHP) cells. Nanoparticles functionalized with CD8− targeting DARPins (CDS-DARPin) can deliver genes exclusively and specifically to human CD8.sup.+ T cells in vitro and in vivo.

In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The medicant moiety can be a toxin including an acylfulvene or a drug moiety. The affinity moiety can be an antibody, a binding protein, a steroid, a lipid, a growth factor, a protein, a peptide or non peptidic. The affinity moiety can be covalently bound to the medicant via a linker. Novel linkers that can be directed to cysteine, arginine or lysine residues based on solution pH allow greater flexibility in preserving and/or generating specific epitopes in the AMC.

In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The medicant moiety can be a toxin including an acylfulvene or a drug moiety. The affinity moiety can be an antibody, a binding protein, a steroid, a lipid, a growth factor, a protein, a peptide or non peptidic. The affinity moiety can be covalently bound to the medicant via a linker. Novel linkers that can be directed to cysteine, arginine or lysine residues based on solution pH allow greater flexibility in preserving and/or generating specific epitopes in the AMC.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

Use of ligand-bound copper clusters (CuCs) and composition comprising the ligand-bound CuCs to treat liver cirrhosis in a subject. Use of ligand-bound copper clusters (CuCs) to manufacture a medication for the treatment of liver cirrhosis in a subject.

Use of ligand-bound copper clusters (CuCs) and composition comprising the ligand-bound CuCs to treat liver cirrhosis in a subject. Use of ligand-bound copper clusters (CuCs) to manufacture a medication for the treatment of liver cirrhosis in a subject.

The present disclosure provides an anti-tumor polypeptide Bax-BH3, a fluorescent polymeric nanomicelle, a preparation method and use thereof, belonging to the technical field of medicines. The anti-tumor polypeptide Bax-BH3 has an amino acid sequence set forth in SEQ ID No: 1; the fluorescent polymeric nanomicelle includes the anti-tumor polypeptide Bax-BH3 and a polymer carrier; and the polymer carrier is a block copolymer RGD-PHPMA-b-Poly(MMA-alt-(Rhob-MA)). In the present disclosure, the anti-tumor polypeptide Bax-BH3 has desirable biocompatibility and biological activity; and the fluorescent polymeric nanomicelle encapsulates the anti-tumor polypeptide Bax-BH3 by the block copolymer RGD-PHPMA-b-Poly(MMA-alt-(Rhob-MA)), with high encapsulation rate and drug loading, and good release performance.

Disclosed are a type of mitochondria-targeted polypeptides, the preparation method and the uses thereof. The polypeptide is abbreviated as MTP. The synthesis method of the present disclosure is simple, and the mitochondria-targeted polypeptide prepared by the method can specifically target the mitochondria of cells and are basically non-toxic to cells. In addition, these synthesized polypeptides demonstrate good cell-membrane-penetrating properties, and can conveniently undergo further multi-functional derivation and modification, thereby providing a potential delivery tool for the preparation of a mitochondria-targeted medicament.

Disclosed are a type of mitochondria-targeted polypeptides, the preparation method and the uses thereof. The polypeptide is abbreviated as MTP. The synthesis method of the present disclosure is simple, and the mitochondria-targeted polypeptide prepared by the method can specifically target the mitochondria of cells and are basically non-toxic to cells. In addition, these synthesized polypeptides demonstrate good cell-membrane-penetrating properties, and can conveniently undergo further multi-functional derivation and modification, thereby providing a potential delivery tool for the preparation of a mitochondria-targeted medicament.