The disclosure features isolated polynucleotides, such as mRNAs, encoding a polypeptide that disrupts immune cell activity, such as T cell or B cell activity, including mRNAs comprising one or more modified nucleobase. The immune cell disruptor polynucleotides encode a polypeptide that comprises a first domain that mediates association of the polypeptide with an immune cell component and a second domain that mediates inhibition of immune cell activity when the polypeptide is expressed in the immune cell. The disclosure also features methods of using the same, for example, for inhibiting immune responses when administered to a subject, such as to inhibit autoimmune reactions.

This invention relates to polynucleotides comprising optimized FIG4 open reading frame (ORF) sequences, vectors comprising the same, and methods of using the same for delivery of the ORF to a cell or a subject and to treat disorders associated with aberrant expression of a FIG4 gene or aberrant activity of a FIG4 gene product in the subject, such as CMT4J.