The invention provides novel PEGylated interferon tau and therapeutic uses thereof. More particularly, the invention provides novel PEGylated interferon tau compositions, methods of their preparation, and methods of therapeutic use thereof in treating viral infections (e.g., coronavirus or flavivirus infections) and various other diseases and conditions.

In certain aspects, the disclosure relates to a nucleic acid molecule encoding two or more different thanotransmission polypeptides. Thanotransmission is communication between cells that is a result of activation of a cell turnover pathway in a target cell, which signals a responding cell to undergo a biological response. Vectors (e.g., engineered viruses, plasmids and transposons), cells and pharmaceutical compositions comprising one or more nucleic acid molecules encoding two or more thanotransmision polypeptides are also disclosed. Methods of promoting thanotransmission by a target cell, methods of promoting an immune response in a subject, and methods of treating cancer in a subject are further disclosed.

In certain aspects, the disclosure relates to a nucleic acid molecule encoding two or more different thanotransmission polypeptides. Thanotransmission is communication between cells that is a result of activation of a cell turnover pathway in a target cell, which signals a responding cell to undergo a biological response. Vectors (e.g., engineered viruses, plasmids and transposons), cells and pharmaceutical compositions comprising one or more nucleic acid molecules encoding two or more thanotransmision polypeptides are also disclosed. Methods of promoting thanotransmission by a target cell, methods of promoting an immune response in a subject, and methods of treating cancer in a subject are further disclosed.

A method of treating a tumor in a subject including administering a genetically modified mesenchymal stem cell (MSC), wherein the MSC includes one or more exogenous nucleic acid molecule(s), wherein the one or more exogenous nucleic acid molecule(s) includes one or more regions encoding two or more immune response-stimulating cytokines operably linked to one or more promoters or promoter/enhancer combinations, wherein the two or more immune response-stimulating cytokines include at least IL-7, and at least one of IL-12 or IL-21.

A method of treating a tumor in a subject including administering a genetically modified mesenchymal stem cell (MSC), wherein the MSC includes one or more exogenous nucleic acid molecule(s), wherein the one or more exogenous nucleic acid molecule(s) includes one or more regions encoding two or more immune response-stimulating cytokines operably linked to one or more promoters or promoter/enhancer combinations, wherein the two or more immune response-stimulating cytokines include at least IL-7, and at least one of IL-12 or IL-21.

A method of inhibiting neutrophil activation in retinal pigment epithelial (RPE) cells comprising administering an inhibitor of interferon (IFN) λ to a subject in need thereof, as well as a method of restoring lysosomal function of RPE cells comprising administering a polypeptide comprising βA1-crystallin or a nucleic acid encoding the polypeptide to a subject in need thereof, are provided. A method of rejuvenating Vacuolar-type H.sup.+-ATPase (V-ATPase) activity in RPE cells by modulating assembly and disassembly of the V-ATPase in a subject in need thereof also is provided. Additionally, a method of treating diabetic retinopathy in a subject comprising administering a polypeptide comprising βA1-crystallin or a nucleic acid encoding the polypeptide to the subject is provided.

Disclosed are a novel interferon lambda variant produced through structure-based glycoengineering and a method of producing the same. The novel interferon lambda variant and the method of producing the same exhibit remarkably improved production and yield in mammalian cell lines using structural information-based glycoengineering even through conventional purification protocols, and exhibit significantly improved therapeutic properties such as stability, half-life, and fraction of functional proteins during treatment, compared to wild-type interferon lambda. In addition, the novel interferon lambda variant and the method of producing the same according to the present invention have higher antiviral activity and interferon-stimulated gene (ISG)-inducing activity than wild-type interferon lambda, and thus are useful for the prevention and treatment of immune-related diseases such as cancer and autoimmune diseases as well as various viral infections such as infection with SARS-CoV-2 (COVID-19).

Disclosed are a novel interferon lambda variant produced through structure-based glycoengineering and a method of producing the same. The novel interferon lambda variant and the method of producing the same exhibit remarkably improved production and yield in mammalian cell lines using structural information-based glycoengineering even through conventional purification protocols, and exhibit significantly improved therapeutic properties such as stability, half-life, and fraction of functional proteins during treatment, compared to wild-type interferon lambda. In addition, the novel interferon lambda variant and the method of producing the same according to the present invention have higher antiviral activity and interferon-stimulated gene (ISG)-inducing activity than wild-type interferon lambda, and thus are useful for the prevention and treatment of immune-related diseases such as cancer and autoimmune diseases as well as various viral infections such as infection with SARS-CoV-2 (COVID-19).

Provided is a genetically engineered immune effector cell, wherein the immune effector cell expresses a receptor specifically recognizing a target antigen and IL7, and the IL-7 is inducibly expressed and regulated by the receptor. Further provided are a nucleic acid molecule expressing the receptor and IL7 in the immune effector cell and a method for preparing the immune effector cell.

Provided is a genetically engineered immune effector cell, wherein the immune effector cell expresses a receptor specifically recognizing a target antigen and IL7, and the IL-7 is inducibly expressed and regulated by the receptor. Further provided are a nucleic acid molecule expressing the receptor and IL7 in the immune effector cell and a method for preparing the immune effector cell.