Abstract: Disclosed herein are compounds that selectively bind an expanded transcribed repeat r(G4C2)exp, prevent sequestration of RNA-binding proteins, and inhibit translation of repeat associated non-ATG (RAN) translation responsible for generation of toxic dipeptide repeats underlying diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The compounds and their pharmaceutical compositions are useful in treating a disease or condition characterized by an expanded G4C2 repeat RNA (r(G4C2)exp), such as ALS and FTD.

Abstract: Autoregulatory systems that have been implemented to control the expression and activity of Cast 3d, including the activity of Cast 3d in vivo, thereby reducing collateral damage in cells at off-target sites (e.g., non-target messenger RNA transcripts. The autoregulatory system is in the form of a nucleic acid molecule comprising a zinc finger binding site, a promoter, and a nucleotide sequence encoding a Cast 3d fusion protein, and a transcriptional repressor domain, and wherein the Cast 3d fusion protein binds to the zinc finger binding site and represses transcription of the nucleotide sequence encoding the Cast 3d fusion protein.

Abstract: The invention is directed towards compounds (e.g., Formulae (I)-(IX)), their mechanism of action, processes to prepare the compounds, methods of activating quorum sensing signaling activity, and methods of treating diseases and disorders using the compounds described herein (e.g., Formulae (I)-(IX)).

Abstract: Disclosed herein are compositions and methods of improving transduction efficiency of rAAV administered to a subject using essential metal elements.

Abstract: Aspects of the disclosure relate to methods and compositions (e.g., kits) for detecting repeat-associated non-ATG (RAN) proteins in a subject (e.g., a subject having or suspected of having a disease associated with RAN protein translation, for example amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD), or spinocerebellar ataxia type 36 (SCA36), or other diseases that produce poly(PR), poly(GR) or poly(GP) RAN proteins. In some embodiments, methods described by the disclosure comprise detecting one or more RAN proteins in a biological sample obtained from a subject by an electrochemiluminescence-based immunoassay using one or more anti-RAN protein antibodies. In some embodiments, the disclosure relates to kits comprising one or more anti-RAN antibodies and an electrochemiluminescence-based immunoassay plate and/or reagents.