	US 12,344,839 B2
	Dual-acting siRNA based modulation of C9orf72
Anastasia Khvorova, Westborough, MA (US); Bruno Miguel da Cruz Godinho, Worcester, MA (US); and James W. Gilbert, Worcester, MA (US)
Assigned to UNIVERSITY OF MASSACHUSETTS, Westborough, MA (US)
Filed by UNIVERSITY OF MASSACHUSETTS, Boston, MA (US)
Filed on Mar. 26, 2021, as Appl. No. 17/213,887.
Claims priority of provisional application 63/000,899, filed on Mar. 27, 2020.
Prior Publication US 2021/0340535 A1, Nov. 4, 2021
Int. Cl. C12N 15/113 (2010.01); C12Q 1/68 (2018.01)

CPC C12N 15/113 (2013.01) [C12N 2310/11 (2013.01); C12N 2310/314 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/3233 (2013.01); C12N 2310/332 (2013.01); C12N 2310/351 (2013.01); C12N 2320/30 (2013.01)]

32 Claims

1. A double-acting RNA silencing agent comprising a first oligonucleotide strand and a second oligonucleotide strand, each strand comprising a 5′ end and a 3′ end, wherein the first strand inhibits expression of a C9ORF72 sense transcript and the second strand inhibits expression of a C9ORF72 antisense transcript, wherein the first and second oligonucleotide strand are substantially complementary to a non-repeat region in the C9ORF72 sense and antisense transcript, respectively;

wherein nucleotides at positions 2-6 and 14 from the 3′ end of the second oligonucleotide strand are 2′-methoxy-ribonucleotides.