The present disclosure relates to nucleic acid promoter sequences that are able to specifically express genes operatively linked to the promoter in brainstem and spinal motor neuron cells, and to methods for using such promoters to selectively express genes in motor neurons in vitro and in vivo. It is based, at least in part, on the discovery that the nucleic acid of SEQ ID NO: 1 functioned as a motor neuron-specific promoter and was successful in expressing transgenes in motor neuron cells in vivo. The present disclosure also relates to compositions that can increase the activity or expression level of miR-218 and to compositions that can decrease the expression of miR-218 target nucleic acids.

The present disclosure provides codon optimized Factor VIII sequences, vectors, and host cells comprising codon optimized Factor VIII sequences, polypeptides encoded by codon optimized Factor VIII sequences, and methods of producing such polypeptides. The present disclosure also provides methods of treating bleeding disorders such as hemophilia comprising administering to the subject a codon optimized Factor VIII nucleic acid sequence or the polypeptide encoded thereby.

Disclosed herein is a composition including a recombinant nucleic acid sequence that encodes an antibody. Also disclosed herein is a method of generating a synthetic antibody in a subject by administering the composition to the subject. The disclosure also provides a method of preventing and/or treating disease in a subject using said composition and method of generation.

Provided herein are methods and compositions for editing the genome of a cell. In some embodiments, a nucleotide sequence of at least 200 nucleotides in length is inserted into a target region in the genome of a cell.

A vibration monitoring system includes a plurality of encoders and an analyzer. The encoders are configured to generate multiple pulse train signals for multiple wheels. Each encoder is coupled to a respective one of the multiple wheels and generates a single one of the pulse train signals. The analyzer is coupled to the encoders and is configured to generate multiple pulse per revolution signals and multiple angular velocity signals for the wheels in response to the pulse train signals. Each pulse per revolution signal conveys a single pulse per rotation of the respective wheel. The analyzer is further configured to generate an input phasor array representative of the pulse per revolution signals, generate a response phasor array in response to the angular velocity signals for the wheels, and generate a report that identifies at least one vibrating wheel in response to the input phasor array and the response phasor array.

The disclosure relates to methods and compositions for reactivating a silenced FMR1 gene. In some aspects, methods described by the disclosure are useful for treating a FMR1-inactivation-associated disorder (e.g., fragile X syndrome).

Methods for treating, and for identifying novel treatments for, neurodegenerative diseases, as well as animal and cellular models.

The application describes ceDNA vectors having linear and continuous structure for gene editing. ceDNA vectors comprise an expression cassette flanked by two ITR sequences, where the expression cassette encodes a gene editing molecule. Some ceDNA vectors further comprise cis-regulatory elements, including regulatory switches. Further provided herein are methods and cell lines for reliable gene editing using the ceDNA vectors.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina for the treatment of retinal disorders and diseases.

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