Abstract: The present invention relates to polyplexes comprising linear conjugates of LPEI and PEG. The LPEI and PEG fragments of the linear conjugates are preferably linked by a [3+2] cycloaddition between an azide and an alkene or an alkyne to produce a 1, 2, 3 triazole or a 4,5-dihydro-1H-[1,2,3]triazole. The linear conjugates are preferably further conjugated to a targeting fragment to enable selective interaction with a particular cell type. The conjugates can form polyplexes with therapeutic agents such as nucleic acids to deliver the therapeutic agents to cells.

Abstract: The present invention relates to a polyplex for use in the treatment of castration resistant prostate cancer (CRPC) comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEI), one or more polyethylene glycol (PEG) moieties, one or more linkers and one or more targeting moieties, wherein said LPEI is covalently bound to one or more PEG moieties and each of said one or more PEG moieties is conjugated via one of the one or more linkers to one of the one or more targeting moieties, wherein each of said one or more targeting moieties is capable of binding to a cancer antigen, and wherein said cancer antigen is prostate surface membrane antigen (PSMA). Further, the invention relates to a pharmaceutical composition for use in the treatment of CRPC.

Abstract: The present invention relates to a kit-of-parts comprising and a composition comprising a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate comprising a polyethyleneimine (PEI), one or more polyethylene glycol (PEG) moieties and one or more targeting moieties, and wherein each of said one or more targeting moieties is capable of 5 binding to PSMA; and at least one least one immune checkpoint modulator, wherein said at least one least one immune checkpoint modulator is capable of modulating an immune checkpoint protein. Further the invention relates to this composition or kit-of-parts for use in the treatment of cancer.

Abstract: The present invention relates to a polyplex for use in the treatment of castration resistant prostate cancer (CRPC) comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEl), one or more polyethylene glycol (PEG) moieties, one or more linkers and one or more targeting moieties, wherein said LPEl is covalently bound to one or more PEG moieties and each of said one or more PEG moieties is conjugated via one of the one or more linkers to one of the one or more targeting moieties, wherein each of said one or more targeting moieties is capable of binding to a cancer antigen, and wherein said cancer antigen is prostate surface membrane antigen (PSMA). Further, the invention relates to a pharmaceutical composition for use in the treatment of CRPC.

Abstract: A method of treating cancer may include administering a polyplex of a double stranded RNA and a polymeric conjugate. The polymeric conjugate may consist of a linear polyethyleneimine covalently linked to one or more polyethylene glycol (PEG) moieties. Each PEG moiety may be conjugated via a linker to a targeting moiety capable of binding to a cancer antigen.

Abstract: The present invention relates to a kit-of-parts comprising and a composition comprising a polyplex comprising a double stranded RNA (dsRNA) and a polymeric conjugate comprising a polyethyleneimine (PEI), one or more polyethylene glycol (PEG) moieties and one or more targeting moieties, and wherein each of said one or more targeting moieties is capable of binding to a cancer antigen; and at least one antibody, wherein said at least one antibody is capable of modulating an immune checkpoint protein. Further the invention relates to this composition or kit-of-parts for use in the treatment of cancer.

Abstract: A method of treating cancer can include administering a polyplex of a double stranded RNA and a polymeric conjugate. The polymeric conjugate can consist of a linear polyethyleneimine covalently linked to one or more polyethylene glycol (PEG) moieties. Each PEG moiety can be conjugated via a linker to a targeting moiety capable of binding to a cancer antigen.

Abstract: The present invention relates to a polyplex for use in the treatment of castration resistant prostate cancer (CRPC) comprising a double stranded RNA (dsRNA) and a polymeric conjugate, wherein said polymeric conjugate consists of a linear polyethyleneimine (LPEl), one or more polyethylene glycol (PEG) moieties, one or more linkers and one or more targeting moieties, wherein said LPEl is covalently bound to one or more PEG moieties and each of said one or more PEG moieties is conjugated via one of the one or more linkers to one of the one or more targeting moieties, wherein each of said one or more targeting moieties is capable of binding to a cancer antigen, and wherein said cancer antigen is prostate surface membrane antigen (PSMA). Further, the invention relates to a pharmaceutical composition for use in the treatment of CRPC.

Abstract: A polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate consists of a linear polyethyleneimine (PEI) covalently linked to one or more polyethylene glycol (PEG) moieties. Each PEG moiety is conjugated via a linker to a targeting moiety capable of binding to a cancer antigen. Exemplary cancer antigens include epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2) and prostate surface membrane antigen (PSMA).

Abstract: A method of treating cancer can include administering a polyplex of a double stranded RNA and a polymeric conjugate. The polymeric conjugate can consist of a linear polyethyleneimine covalently linked to one or more polyethylene glycol (PEG) moieties. Each PEG moiety can be conjugated via a linker to a targeting moiety capable of binding to a cancer antigen.

Abstract: A polyplex of a double stranded RNA (dsRNA) and a polymeric conjugate consists of a linear polyethyleneimine (PEI) covalently linked to one or more polyethylene glycol (PEG) moieties. Each PEG moiety is conjugated via a linker to a targeting moiety capable of binding to a cancer antigen. Exemplary cancer antigens include epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2) and prostate surface membrane antigen (PSMA).

Abstract: A polyplex of a double stranded RNA and a polymeric conjugate is provided, wherein the polymeric conjugate consists of a linear polyethyleneimine covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen.

Abstract: A polyplex of a double stranded RNA and a polymeric conjugate is provided, wherein the polymeric conjugate consists of a linear polyethyleneimine covalently linked to one or more polyethylene glycol (PEG) moieties, each PEG moiety being conjugated via a linker to a targeting moiety capable of binding to a cancer antigen.