Methods and compositions capable of modulating activity of TLX (NR2E1), a nuclear receptor essential for neural stem cell self-renewal are provided. The modulation may comprise downregulating TLX expression and/or modulating TET3. In addition, methods of delivering shRNAs using dendrimer nanoparticles into glioblastoma stem cells are provided. The methods and compositions are useful for treating and preventing the progression of brain cancer, e.g., glioblastoma.

The present invention provides nucleic acid aptamers binding to the Carbonic Anhydrase IX (CA-IX) enzyme, derivatives and conjugates thereof and their use as diagnostic tools, particularly for the imaging of organs and tissues expressing CA-IX, or as therapeutic agents for prevention or treatment of CA-IX related diseases.

The present disclosure provides compositions and methods for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap, which is homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incorporated into the target DNA molecule. Also disclosed herein are various methods that leverage prime editing, including treating trinucleotide repeat contraction diseases, installing targeted peptide tags, treating prion disease through the installation of protection mutations, manipulating RNA-encoding genes for the installation of RNA tags for controlling the function and expression of RNA, using prime editing to construct sophisticated gene libraries, using prime editing to insert immunoepitopes into proteins, use of prime editing to insert inducible dimerization domains into protein targets, and delivery methods, among others.

Disclosed herein are compositions and methods for labeling cells using click chemistry reagents. The compositions and methods disclosed herein provide a specific and efficient means of localizing desired agents to a variety of cell types in vivo and in vitro. The compositions and methods disclosed herein can be used to deliver a variety of desired agents to a cell or population of cells to direct cell fate and/or cell differentiation.

Improved compositions and methods for treating a disease or disorder through target exon skipping, and preferably muscular dystrophy by administering antisense thiomorpholino molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping to produce a functional Dystrophin protein.

The disclosure is directed to conjugates, e.g. PNA conjugates, as well as methods of employing the conjugates for detecting one or more targets in a biological sample, e.g. a tissue sample.

Provided herein are compositions and methods for sorting and/or identifying live cells. The compositions and methods provide for staining of live cells with aptamer so particular cells can be identified within or sorted from a heterogeneous population of live cells and subsequent reversal of the staining to prepare sorted and/or identified cells in their native state.

The invention provides eukaryotic cell-based screening methods to identify an aptamer that specifically binds a ligand, or a ligand that specifically binds an aptamer, using a polynucleotide cassette for the regulation of the expression of a reporter gene where the polynucleotide cassette contains a riboswitch in the context of a 5′ intron-alternative exon-3′ intron. The riboswitch comprises an effector region and an aptamer such that when the aptamer binds a ligand, reporter gene expression occurs.

The present disclosure provides materials and methods for the continuous measurement of biomolecules in vivo and in real-time. The present disclosure relates more specifically to using capture agents and detection agents within a microfluidic device to detect and quantify biochemical features of biomarkers, enabling real-time detection and concentration measurements.

The present invention serves as a platform technology to deliver RNA therapeutics into cells. It provides a system for delivery of RNA molecules for biomedical purposes. The modular protein-based system described in this invention allows for customization of protein modules to achieve specificity in cell-targeting, thus having the ability to be optimized for treating different diseases. Examples of types of diseases that could adopt this technology for treatment include cancer, neurodegenerative diseases and viral infection.