US 11,926,829 B2
Allele-specific silencing therapy for dynamin 2-related diseases
Marc Bitoun, Villejuif (FR); Delphine Trochet, Villejuif (FR); and Bernard Prudhon, Paris (FR)
Assigned to ASSOICATION INSTITUT DE MYOLOGIE, Paris (FR); INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE), Paris (FR); SORBONNE UNIVERSITE, Paris (FR); and CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE, Paris (FR)
Filed by ASSOCIATION ISNTITUT DE MYOLOGIE, Paris (FR); INSERM (INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE), Paris (FR); SORBONNE UNIVERSITE, Paris (FR); and CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (CNRS), Paris (FR)
Filed on Feb. 3, 2021, as Appl. No. 17/166,377.
Application 17/166,377 is a division of application No. 16/464,482, granted, now 10,947,540, previously published as PCT/EP2017/080884, filed on Nov. 19, 2017.
Claims priority of application No. 16306575 (EP), filed on Nov. 19, 2016.
Prior Publication US 2021/0163953 A1, Jun. 3, 2021
Int. Cl. C12N 15/113 (2010.01)
CPC C12N 15/1137 (2013.01) [C12N 2310/14 (2013.01); C12N 2320/34 (2013.01); C12Y 306/05005 (2013.01)] 9 Claims
 
1. An allele specific siRNA (AS-siRNA) that comprises a sequence mismatch and is able to silence the expression of only one allele of a heterozygous DNM2 gene in a cell, wherein the DNM2 gene is heterozygous for the presence of a disease-causing mutation, wherein said AS-siRNA targets a region of a human DNM2 gene transcript comprising said disease-causing mutation, wherein the disease-causing mutation is 1393C>T; c.1105C>T, c.1106G>A, c.1856C>T or c.1948G>A, and wherein the AS-siRNA comprises a sense strand and an antisense strand and the antisense strand only contains bases selected from the group consisting of guanine, cytosine, adenine, uracil, and deoxythymidine.