Abstract: Provided herein, inter alia, are expression systems capable of modulating expression of MECP2. In embodiments, the expression systems silence the expression of endogenous MECP2 and induce expression of recombinant MECP2. The expression system provided herein may be useful for treating a genetic disorder such as Rett Syndrome.

Abstract: Disclosed herein are systems for modifying nucleic acid splicing of a target RNA. The system may be useful in a method such as a method for treating a genetic disorder such as epilepsy. The system may include an expression system, or a modified small nuclear RNA (snRNA) that includes an exonic splicing silencer (ESS) sequence, and a target nucleic acid sequence that targets the target RNA. Described herein are recombinant regulatory elements for expression systems. Also described are nucleic acid expression systems with recombinant regulatory elements.

Abstract: Disclosed herein are systems for modifying nucleic acid splicing of a target RNA such as an SCN1A mRNA. The system may be useful in a method such as a method for treating a genetic disorder such as epilepsy. The system may include an expression system, or a modified small nuclear RNA (snRNA) that includes an exonic splicing silencer (ESS) sequence, and an antisense nucleic acid sequence that targets the target RNA.

Abstract: Provided herein, inter alia, are expression systems capable of modulating expression of a target gene. In embodiments, the expression systems silence the expression of an endogenous version of the gene and induce expression of a recombinant version of the gene. The expression system provided herein is contemplated to be effective for treating genetic disorders.