Intein-mediated reconstitution of voltage-gated sodium channel function
AssigneesAllen Institute, Seattle Children’s Hospital d/b/a Seattle Children’s Research Institute
InventorsBryan Gore, Edward Sebastian Lein, Boaz P. Levi, Refugio Martinez, John K. Mich, Franck Kalume
Life of this patent
Estimating the term…
Abstract
Artificial expression constructs for the rescue of voltage-gated sodium channel function using intein-mediated reconstitution of the SCN1A encoded protein, voltage-gated sodium channel alpha subunit 1 (Nav1.1) are described. Rescued voltage-gated sodium channel function can be used to treat disorders such as epilepsy, and more particularly, Dravet Syndrome.
Claims115
A system to express a functional SCN1A protein in a subject in need thereof comprising
- (i) a first artificial expression construct comprising
- a first portion of an SCN1A coding sequence, the first portion having the sequence as set forth in SEQ ID NO:
- 59;
- an N-intein coding sequence as set forth in SEQ ID NO:
- 57;
- and
- a first promoter sequence;
- wherein the N-intein coding sequence is located at the 3′ end of the first portion of the SCN1A coding sequence;
- and
- (ii) a second artificial expression construct comprising
- a second portion of the SCN1A coding sequence, the second portion having the sequence as set forth in SEQ ID NO:
- 60;
- a C-intein coding sequence as set forth in SEQ ID NO:
- 58;
- and
- a second promoter sequence;
- wherein the C-intein coding sequence is located at the 5′ end of the second portion of the SCN1A coding sequence;
- wherein when the first artificial expression construct and the second artificial expression construct are expressed in a central nervous cell type, the protein product of the first portion of the SCN1A coding sequence and the protein product of the second portion of the SCN1A coding sequence are linked to form the functional SCN1A protein within the central nervous cell type.
A system to express a functional SCN1A protein in a subject in need thereof comprising
- (i) a first artificial expression construct comprising a first portion of an SCN1A coding sequence, an N-intein coding sequence, and a first promoter sequence, wherein the N-intein coding sequence is located at the 3′ end of the first portion of the SCN1A coding sequence;
- and
- (ii) a second artificial expression construct comprising a second portion of the SCN1A coding sequence, a C-intein coding sequence, and a second promoter sequence, wherein the C-intein coding sequence is located at the 5′ end of the second portion of the SCN1A coding sequence;
- wherein when the first artificial expression construct and the second artificial expression construct are expressed in a central nervous cell type, the protein product of the first portion of the SCN1A coding sequence and the protein product of the second portion of the SCN1A coding sequence are linked to form the functional SCN1A protein within the central nervous cell type.
An artificial expression construct comprising a portion of an SCN1A coding sequence, an N-intein coding sequence, and a promoter sequence, wherein the N-intein coding sequence is located at the 3′ end of the portion of the SCN1A coding sequence.
An artificial expression construct comprising a portion of an SCN1A coding sequence, a C-intein coding sequence, an enhancer sequence that leads to targeted expression of the portion of the SCN1A coding sequence within a targeted central nervous system cell type, and a promoter sequence, wherein the C-intein coding sequence is located at the 5′ end of the portion of the SCN1A coding sequence.
An artificial expression construct comprising CN3252, CN3254, CN3683, CN3684, CN3251, CN3253, CN3677, CN3678, CN4541, CN4542, CN4217, CN4218, CN4642, or CN4643.
Dependencies are inferred from the claim text.