US 11,655,470 B2
Diagnosing COL6-related disorders and methods for treating same
Carsten G. Bonnemann, Washington, DC (US); Veronique Bolduc, Rockville, MD (US); Francesco Muntoni, London (GB); Steve Wilton, Applecross (AU); Daniel Macarthur, Cambridge, MA (US); Monkol Lek, Braintree, MA (US); and Beryl Cummings, Brookline, MA (US)
Assigned to The USA, as represented by the Secretary, Dept. of Health and Human Services, Bethesda, MD (US)
Appl. No. 16/315,278
Filed by THE USA, AS REPRESENTED BY THE SECRETARY, DEPT. OF HEALTH AND HUMAN SERVICES, Bethesda, MD (US); MURDOCH UNIVERSITY, Perth (AU); THE GENERAL HOSPITAL CORPORATION, Boston, MA (US); PRESIDENT AND FELLOWS OF HARVARD COLLEGE, Cambridge, MA (US); and UCL BUSINESS PLC, London (GB)
PCT Filed Jul. 5, 2017, PCT No. PCT/US2017/040726
§ 371(c)(1), (2) Date Jan. 4, 2019,
PCT Pub. No. WO2018/009547, PCT Pub. Date Jan. 11, 2018.
Claims priority of provisional application 62/358,482, filed on Jul. 5, 2016.
Prior Publication US 2019/0367917 A1, Dec. 5, 2019
Int. Cl. C12N 15/113 (2010.01); C12N 15/86 (2006.01); C12Q 1/6883 (2018.01)
CPC C12N 15/113 (2013.01) [C12N 15/86 (2013.01); C12Q 1/6883 (2013.01); C12N 2310/11 (2013.01); C12N 2310/3233 (2013.01); C12N 2320/33 (2013.01); C12N 2800/60 (2013.01); C12Q 2600/156 (2013.01)] 8 Claims
 
1. A synthetic antisense oligomer that
a) comprises a sequence selected from the group consisting of SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, and SEQ ID NO:44;
wherein the antisense oligomer consists of a number of monomers no more than 5 monomers greater than its respective SEQ ID NO; or
b) consists of a sequence of monomers identical to a sequence comprised by one of SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, and SEQ ID NO:44, where said sequence of monomers is not less than 5 monomers shorter than its respective SEQ ID NO,
wherein the antisense oligomer is an antisense RNA molecule having a chemical modification that increases its affinity for its target RNA, increases its nuclease resistance, and/or alters its pharmacokinetics,
wherein the chemical modification is selected from the group consisting of;
substitution of a sugar for a sugar mimetic or sugar analog, substitution of a sugar-internucleoside linkage combination for an analog or mimetic; substitution of a nucleobase for an analog or mimetic; and, any combination thereof,
and wherein the presence of the antisense oligomer in a splicing reaction comprising a COL6A1 pre-mRNA molecule having a non-native splice donor site in intron 11, results in normal splicing of the COL6A1 pre-mRNA molecule.