The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding an immunomodulatory polypeptide (e.g., a pro-inflammatory cytokine such as a human IL-2 or IL-12 polypeptide); viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of cancer, such as lung cancer); and articles of manufacture or kits thereof.

The disclosure relates to a biosensor on the bacterial cell surface for sensing and responding to extracellular molecules. Related methods of using the bacterial cells to inducibly express a protein of interest and/or a bioactive RNA molecule in a subject are disclosed. Related methods of using the bacterial cells to inducibly express a protein of interest or to detect a target of interest in a sample are also disclosed.

The present invention refers to hyperactive variants of a transposase of the transposon system Sleeping Beauty (SB). The invention further refers to corresponding nucleic acids producing these variants, to a gene transfer system for stably introducing nucleic acid(s) into the DNA of a cell by using these hyperactive variants of a transposase of the transposon system Sleeping Beauty (SB) and to transposons used in the inventive gene transfer system, comprising a nucleic acid sequence with flanking repeats (IRs and/or RSDs). Furthermore, applications of these transposase variants, the transposon, or the gene transfer system are also disclosed such as gene therapy, insertional mutagenesis, gene discovery (including genome mapping), mobilization of genes, library screening, or functional analysis of genomes in vivo and in vitro. Finally, pharmaceutical compositions and kits are also encompassed.

The present invention relates to an RNA suitable for treatment or prophylaxis of liver diseases. In particular, the present invention provides an RNA encoding at least one peptide or protein selected from the group consisting of an extracellular matrix protease, CCAAT/enhancer-binding protein alpha (CEBPA), TNF-related apoptosis-inducing ligand (TRAIL), Hepatocyte Growth Factor (HGF), hepatocyte nuclear factor 4 alpha (HNF4A), fibroblast growth factor 21 (FGF21), opioid growth factor receptor-like 1 (OGFRL1), Relaxin 1 (RLN1), Relaxin 2 (RLN2) and Relaxin 3 (RLN3), or a fragment or a variant of any of these peptides or proteins. The present invention concerns said RNA as well as compositions and kits comprising the RNA. Furthermore, the present invention relates to the RNA, compositions or kits as disclosed herein for use as a medicament, in particular for treatment or prophylaxis of a liver disease. The present invention also provides the use of the RNA, compositions or kits as disclosed herein for increasing the expression of said encoded protein, in particular in gene therapy.

Provided herein are methods, systems, and related vectors and compositions allowing for noninvasive control of neural circuits. In particular, the methods and systems herein described utilize acoustically targeted chemogenetics to achieve a noninvasive neuromodulation in specifically selected cell-types among spatially selected brain regions.

In certain embodiments methods of treating X-Linked Hyper-IgM Syndrome (XHIM) in a mammal am provided where the methods comprise: i) providing differentiated T cells and/or stem/progenitor cells from the mammal; ii) performing a targeted insertion of a corrective CD40L cDNA at the CD40LG gene locus in said cells to provide a corrected CD40LG gene wherein said targeted insertion places said corrective CD40L cDNA downstream and operably linked to the endogenous CD40LG enhancer/promoter, and iii) introducing said cells into said mammal where said corrected CD40LG gene is expressed in a physiologically regulated manner.

Provided herein are methods of treating a subject with Cockayne Syndrome (CS) or a predisposition thereto. Also provided are methods of treating a subject with one or more mutations in an ERCC5 gene, an ERCC8 gene, an ERCC6 gene, or a combination thereof, methods of delaying the onset of Cockayne Syndrome (CS), or a symptom thereof, in a subject with one or more mutations in an ERCC5 gene, an ERCC8 gene, an ERCC6 gene, or a combination thereof, and methods of slowing, halting or reversing progression of Cockayne Syndrome (CS) in a subject. In exemplary embodiments, the method comprises administering to the subject a replication-incompetent Adeno-associated Vims (riAAV) comprising a nucleotide sequence encoding a Xeroderma Pigmentosum group G (XPG) protein, a Cockayne Syndrome type A (CSA) protein, or a Cockayne Syndrome type B (CSB) protein in an effective amount. Provided herein are related Adeno-associated Virus and cells comprising the same.

Provided herein are compositions for gene modification or editing and methods of using same to treat or prevent certain conditions. Specific compositions and methods capable of safely and effectively editing gene targets expressed in the liver to durably lower LDL-C thereby treating a leading cause of cardiovascular disease are disclosed.

The present disclosure provides codon optimized nucleotide sequences encoding human REP1, vectors, and host cells comprising codon optimized REP1 sequences, and methods of treating retinal disorders such as choroideremia comprising administering to the subject a codon optimized sequence encoding human REP1.

Embodiments of the instant disclosure relate to novel antiviral compositions and methods for treating viral infections. In accordance with these embodiments, antiviral compositions can include at least one mRNA encoding for a TRIM7 protein encapsulated into a lipid nanoparticle (LNP). In other embodiments, methods of making antiviral compositions are disclosed as well as methods of administering a composition having at least one mRNA encoding for a TRIM7 protein encapsulated into LNP into a subject.