This invention relates to polynucleotides comprising a nucleotide sequence encoding a PPT1 polypeptide or a fragment thereof, vectors (viral or non-viral vectors) comprising the same, and methods of using the same for delivery of the open reading frame to a cell or a subject and to treat infantile neuronal lipofuscinosis (infantile Batten disease). The polynucleotides comprise an optimized CLN1 open reading frame.

Nonsense-mediated mRNA decay (NMD) polypeptides, nucleic acids encoding NMD polypeptides, and methods of using such polypeptides and nucleic acids in the treatment of ALS and in screening for agents for the treatment of ALS are described.

Disclosed herein are polynucleotides having a plurality of thymine nucleotides and an endonuclease recognition site inserted therein, methods of engineering the polynucleotides having a plurality of thymine nucleotides and an endonuclease recognition site inserted therein, and methods of enhancing transcription, translation, and increasing stability of a polynucleotide.

The present disclosure provides compositions and methods related to transcription factor systems. Such systems provide for modular and tunable protein expression driven by regulated transcriptional activity.

The present disclosure provides, among other things, a recombinant adeno-associated virus (rAAV) vector comprising an AAV8 capsid and a codon-optimized sequence encoding a human phenylalanine hydroxylase (PAH) enzyme. The disclosure also provides a method of treating a subject having phenylketonuria (PKU), comprising administering to the subject in need thereof a recombinant adeno-associated vims (rAAV) vector comprising an AAV8 capsid, and a promoter operably linked to a nucleic acid sequence that encodes PAH, and wherein administering results in a decrease in phenylalanine level in the subject.

The present application provides materials and methods for treating a patient with one or more conditions associated with ANGPTL4 whether ex vivo or in vivo. In addition, the present application provides materials and methods for editing and/or modulating the expression of ANGPTL4 gene in a cell by genome editing.

The invention provides expression cassettes. In certain embodiments, an expression cassette comprises (a) a regulatory element at least 90% identical to the sequence of any of SEQ ID NOs:2-67, and (b) a nucleic acid sequence encoding a Factor VIII protein having a B domain deletion (FVIII-BDD), where the nucleic acid sequence of (a) is at least 90% identical to the sequence of SEQ ID NO:77, where the regulatory element is operably linked to the nucleic acid sequence, and where no intron is present between the regulatory element and the nucleic acid sequence encoding FVIII-BDD, or where no more than 0-107 nucleotides of untranslated nucleic acid is between the regulatory element and the nucleic acid sequence encoding FVIII-BDD. In certain embodiments, expression cassettes contain sequence elements having CpG(s) substituted with CpT, CpA, TpG, or ApG at the same position(s) or has CpG reduced nucleic acid sequences.

mRNAs containing an exogenous open reading frame (ORF) flanked by a 5′ untranslated region (UTR) and a 3′ UTR is provided, wherein the 5′ and 3′ UTRs are derived from a naturally abundant mRNA in a tissue. Also provided are methods for identifying the 5′ and 3′ UTRs, and methods for making and using the mRNAs.

The present invention provides, among other things, a method of ocular delivery of messenger RNA (mRNA), comprising administering into an eye of a subject in need of delivery a composition comprising an mRNA encoding a protein, such that the administration of the composition results in expression of the protein encoded by the mRNA in the eye.

Materials and methods for producing genome-edited cells engineered to express a chimeric antigen receptor (CAR) construct on the cell surface, and materials and methods for genome editing to modulate the expression, function, or activity of one or more immuno-oncology related genes in a cell, and materials and methods for treating a patient using the genome-edited engineered cells.