Provided herein, in some aspects, are tools (e.g., methods, compositions and nucleic acids) for building genetic circuits in Bacteroides and Parabacteroides bacteria, as well as the bacteria containing the genetic circuits.

Compositions include modified adenoviruses. Nucleotides, cells, and methods associated with the compositions, including their use as vaccines. Viral vectors using a TET promoter system and methods of producing viruses having the same.

Compositions and methods are described for the delivery of a fully human post-translationally modified (HuPTM) monoclonal antibody (“mAb”) or the antigen-binding fragment of a mAb against human vascular endothelial growth factor (“hVEGF”)—such as, e.g., a fully human-glycosylated (HuGly) anti-hVEGF antigen-binding fragment—to the retina/vitreal humour in the eye(s) of human subjects diagnosed with ocular diseases caused by increased neovascularization, for example, neovascular age-related macular degeneration (“nAMD”), also known as “wet” age-related macular degeneration (“WAMD”), age-related macular degeneration (“AMD”), and diabetic retinopathy.

Provided herein are recombinant nucleic acids encoding T cell receptor (TCR) fusion proteins (TFPs), modified human immune cells expressing the encoded molecules, and methods of use thereof for the treatment of diseases, including cancer.

Methods and constructs for engineering circular RNA are disclosed. In some embodiments, the methods and constructs comprise a vector for making circular RNA, the vector comprising the following elements operably connected to each other and arranged in the following sequence: a.) a 5′ homology arm, b.) a 3′ group I intron fragment containing a 3′ splice site dinucleotide, c.) optionally, a 5′ spacer sequence, d.) a protein coding or noncoding region, e.) optionally, a 3′ spacer sequence, f) a 5′ Group I intron fragment containing a 5′ splice site dinucleotide, and g.) a 3′ homology arm, the vector allowing production of a circular RNA that is translatable or biologically active inside eukaryotic cells. Methods for purifying the circular RNA produced by the vector and the use of nucleoside modifications in circular RNA produced by the vector are also disclosed.

The present invention provides polynucleotide vectors for high expression of heterologous genes. Some vectors further comprise novel transposons and transposases that further improve expression. Further disclosed are vectors that can be used in a gene transfer system for stably introducing nucleic acids into the DNA of a cell. The gene transfer systems can be used in methods, for example, gene expression, bioprocessing, gene therapy, insertional mutagenesis, or gene discovery

Aspects of the disclosure relate to compositions and methods for regulation of transgene (e.g., miRNAs, shRNAs or coding sequences) expression from viral vectors. In some embodiments, the disclosure provides expression constructs comprising a viral vector encoding one or more transgenes, the expression of which is regulated by a rapamycin/rapalog-based system.

Disclosed are compositions and methods for treating neurological diseases, disorders, and injuries in a subject in need thereof. Particularly disclosed are compositions and methods for treating neurological diseases, disorders, and injuries that are associated with upper motor neurons in a subject in need thereof in which methods expression of ubiquitin carboxyl hydrolase ligase 1 (UCHL1) is modulated in the subject, for example, via gene therapy being administered to the subject in order to express UCHL1 in upper motor neurons of the subject. Also disclosed are expression vectors comprising the UCHL1 promoter operably linked to a nucleic acid encoding a therapeutic gene product.

The present invention contemplates mRNA, episomal and retroviral genomic gene therapy based short-term, intermediate or long-term vaccine, immunization, protection or therapy—that can also be administered as a retroviral genomic gene therapy—method to provide mucosal and hematological protection to humans to protect against pandemic and non-pandemic viruses, bacterial infections, fungi, allergens or the cause of allergic reactions, systemic pathological conditions, cancer and anti-biowarfare agents (e.g. natural and unnatural viruses and toxins) where mucosal immunity and potentially hematological immunity is achieved through mRNA, episomal or genomic expression of dimeric immunoglobulin A1 (dIgA1) and dimeric immunoglobulin A2 (dIgA2). The present invention provides methods, immunoglobulin compositions and vector constructs to express potent immunoglobulins that are derived from human blood of a human currently infected with, affected by, exposed to or recovered from any of a wide range of allergens or the cause of allergic reactions, pathogens (including, viruses, virus mutants, bacterial infections and fungi) and systemic pathological ailments (including cancer and other disorders), developed from phage display technology or mice or other animals with a humanized immune systems, transgenic mice or chimeric antibodies a fusion of non-human vetebrates (e.g. mouse or rabbit) and human. The immunoglobulin compositions include the heavy chain variable, diversity and joining (VDJ or Variable Heavy Region genes) segment immunoglobulin DNA and/or polypeptide sequence from humans identified to have developed high affinity immunoglobulins against the antigen, protein or proteins of interest and either to use the exact immunoglobulin heavy chain and light chain polypeptide sequences identified from the memory B-cell that produced them or to modify or engineer some of the immunoglobulin heavy chain and light chain constant domains to reduce, change or modulate effector functions. Although, ideally there are no changes made to the immunoglobulins light and heavy chains as identified from the memory B-cell that produced them. Modification may occur at the Hinge region, Constant Heavy 2 (C.sub.H2) domain and Constant Heavy 3 (C.sub.H3) domain for the immunoglobulin heavy chain polypeptide with optional modification or change of Constant Heavy 1 (C.sub.H1), optional modification or change constant light (C.sub.L) chain domain. The resulting antibodies can either be used as a monoclonal or antibody cocktail of (Immunoglobulin Class G subclass1) IgG1, IgG2, IgG3 and other subclasses, IgA1 monomer and IgA2 monomer and dimeric IgA1 (dIgA1) and dimeric IgA2 (dIgA2) immu

The present invention relates to an anti-tumor adenovirus and an anticancer composition comprising same. Double-stranded siRNA of the present invention simultaneously inhibits the expression of a first nucleic acid and a second nucleic acid, thus promoting the death of cancer cells, exhibits more remarkable anticancer activity as compared to co-treatment of respective siRNAs, has a synergistic effect of improving cancer cell death in combined treatment with an anticancer agent. The adenovirus comprising a shRNA-encoding expression cassette expressing the double-stranded siRNA, and a hTERT promoter evades immune responses in the body and is specifically delivered to cancer cells, thus having a systemic therapeutic effect, can be locally delivered, has excellent selectivity, and exhibits a significant anticancer effect even in minimally invasive treatment, and thus, the adenovirus can be effectively used as an anticancer composition or an anticancer adjuvant in various carcinomas.