The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and/or NK cells. The methods can include inhibitory RNA molecule(s) and/or engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and/or genetically modified T cells and/or NK cells are provided, such as, for example, those including riboswitches, MRB-CARs, recognition domains, and/or pH-modulating agents.

This invention relates generally to pharmaceutical compositions and preparations of circular polyribonucleotides and uses thereof.

The presently-disclosed subject matter relates to RNA-based composition and method to treat breast cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a breast cancer targeting module, and an effective amount of a breast cancer therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat breast cancer in a subject having or at risk of having breast cancer.

The invention relates to a method of treating a cardiovascular disease, such as heart failure, in a subject in need comprising the step of administering an inhibitor of bZIP repressor or an activator of p38 or a combination thereof to a subject in need thereby treating the cardiovascular disease. The inhibitor to bZIP repressor is: an inhibitor of ATF3; an inhibitor of JDP2; a co-inhibitor to both ATF3 and JDP2; or a combination of an inhibitor of ATF3 and an inhibitor of JDP2.

Methods of minimizing dysregulation of Staufen1-associated RNA metabolism can include introducing an amount of a Staufen1-regulating agent to a target cell sufficient to minimize the dysregulation. Therapeutic compositions for treating a neurodegenerative condition associated with Staufen1-induced dysregulation of RNA metabolism can include a therapeutically effective amount of a Staufen1-regulating agent and a pharmaceutically acceptable carrier.

The present disclosure, at least in part, provides RNA cleavage based engineered bi-stable toggle switch utilizing the Programmable Endonucleolytic Scission-Induced Stability Tuning (PERSIST) platform. Also provided herein, are vectors encoding the engineered bi-stable toggle switch, and uses thereof.

A method of inhibiting activity or expression of one or more 3α-oxidoreductase enzymes that share a common catalytic site and convert androstanediol to DHT. The method comprises introducing one or more agents into cells that comprise the one or more 3α-oxidoreductase enzymes, wherein said one or more agents: i) inhibit function of one or more of said enzymes; ii) inhibit translation of mRNA encoding said enzymes; iii) disrupt or delete genes encoding said enzymes; or a combination thereof.

The present disclosure provides a pharmaceutical composition for treating or preventing cancer, comprising inhibitors of KIRREL3, CNTN4 and/or CD351. In addition, the present disclosure provides a pharmaceutical composition for immune-enhancing, comprising inhibitors of KIRREL3, CNTN4 and/or CD351. Furthermore, the present disclosure provides a method of screening of anti-cancer agent using KIRREL3, CNTN4 and/or CD351, and a method of providing information necessary for analysis of cancer prognosis using KIRREL3, CNTN4 and/or CD351.

Provided is a system for DNA editing, comprising crRNA and tracrRNA. The crRNA is an RNA shown in formula I: Nx-ncrRNA (formula I), wherein the Nx is a spacer, and the ncrRNA is an RNA shown in SEQ ID NOs. 1-4 of the Sequence Listing. The tracrRNA is an RNA shown in SEQ ID NOs. 5-8 of the Sequence Listing.

The present disclosure provides a method of treating a wasting disorder in a subject, the method comprising administering to the subject a compound that inhibits VEGF-B signalling. The present disclosure also provides a method of treating cancer cachexia in a subject suffering from cancer cachexia, the method comprising 5 administering to the subject a compound that inhibits VEGF-B signaling.