The invention relates to an adenoviral-based biological delivery and expression system for use in the treatment or prevention of osteoarthritis in human or mammalian joints by long-term inducible gene expression of human or mammalian interleukin-I receptor antagonist (IL-1 Ra) in synovial cells, comprising a helper-dependent adenoviral vector containing a nucleic acid sequence encoding for human or mammalian interleukin-I receptor antagonist (IL-I Ra), left and right inverted terminal repeats (L ITR and R ITR), the adenoviral packaging signal and non-viral, non-coding stuffer nucleic acid sequences, wherein the expression of the human or mammalian interleukin-I receptor antagonist (IL-I Ra) gene within synovial cells is regulated by an inflammation-inducible promoter.

Embodiments of the disclosure include methods and compositions for in situ cardiac cell regeneration, including transdifferentiation of cardiac cells to cardiomyocytes. In particular embodiments, in situ cardiac cell regeneration encompasses delivery of p63 shRNA and one or both of Hand2 and myocardin, and in specific embodiments further includes one or more of Gata4, Mef2c, and Tbx5. In specific aspects of the disclosure, adult cardiac fibroblasts are reprogrammed into cardiomyocytes using viral vectors that harbor p63 shRNA and one or both of the transcription factors Hand2 and myocardin.

The present invention relates to an adenoviral vector capable of encoding a virus-like particle (VLP), said VLP displaying an inactive immune-suppressive domain (ISD). The vaccine of the invention shows an improved immune response from either of both of the response pathways initiated by CD4 T cells or CD8 T cells.

The present disclosure provides, in part, a priming and boosting vector-based platform to develop vaccines against pathogens that is tailored to elicit a broad T cell response targeting conserved viral epitopes. The universal vaccines are prepared against an immunogen of an infectious pathogenic organism selected from a virus, a bacteria, a fungus or a protozoan comprising at least one ribonucleic acid (RNA) polynucleotide comprising an open reading frame encoding at least one polypeptide antigen or an immunogenic fragment thereof, wherein the polypeptide antigen, or the immunogenic fragment thereof, comprises a conserved internal protein that is enriched in CD8+ T cell recognition antigens. The effectiveness of the priming and boosting platform is tested in a humanized mouse model comprising a fully functional human immune system.

Provided are an LncRNA and oncolytic adenovirus, and application thereof. The oncolytic adenovirus is used as a carrier to express the LncRNA, so as to express the LncRNA in a cancer cell; competitively binding a target gene of OncomiRs, and consuming the OncomiRs, thus protecting a cancer suppressor gene from interference and suppression of the OncomiRs, and achieving target intervention therapy of the cancer cell.

The present disclosure describes the role for miR-322(424)/503 in the differentiation of cardiac precursor cells. Thus, the use of these molecules in the programming of resident stem/progenitor cells into cardiomyocytes, both in vitro and in vivo. Such methods find particular use in the treatment of patients post-myocardial infarction to prevent or limit scarring and to promote myocardial repair.

Provided herein are improved vaccines for HSV-2.

Provided herein are methods for using compositions that include a fusion protein having a YscF protein domain, a mature F1 protein domain, and a LcrV protein domain. In one embodiment the composition is used to confer immunity to plague, such as pneumonic plague, caused by Yersinia pestis. In one embodiment, the composition is administered to a mucosal surface, such as by an intranasal route. In one embodiment, the administration to a mucosal surface includes a vector that has a polynucleotide encoding a fusion protein, where the fusion protein includes a YscF protein domain, a mature F1 protein domain, and a LcrV protein domain. The administration is followed by a second administration by a different route, such as an intramuscular route. The second administration includes a fusion protein having the same three domains, and in one embodiment the fusion protein is the same one administered to a mucosal surface.

The invention provides a replication-deficient serotype 28 adenoviral vector characterized by comprising a portion of a serotype 45 adenoviral hexon protein and/or a portion of a serotype 45 fiber protein in place of the endogenous serotype 28 hexon and/or fiber protein.

The present invention features methods for stimulating clearance of misfolded or aggregated proteins or peptides in microglia or neurons, and treating neurodegenerative diseases associated with such pathology in brain by selectively inhibiting the expression or activity of Acyl-CoA: Cholesterol Acyltransferase 1, but not Acyl-CoA: Cholesterol Acyltransferase 2.