US 12,410,440 B2
ABCA4 trans-splicing molecules
Rebekka Krumbach, Boston, MA (US); Scott Dooley, Boston, MA (US); Akiko Doi, Boston, MA (US); Kirk Burkhart, Boston, MA (US); Jesse Gray, Boston, MA (US); Lingtao Peng, Boston, MA (US); Dennis Wu, Boston, MA (US); Akiko Noma, Boston, MA (US); Kirk Gosik, Boston, MA (US); Shimyn Slomovic, Boston, MA (US); Adam Clemens, Boston, MA (US); and Robert Bell, Boston, MA (US)
Assigned to Ascidian Therapeutics, Inc., Boston, MA (US)
Filed by Ascidian Therapeutics, Inc., Boston, MA (US)
Filed on Nov. 22, 2023, as Appl. No. 18/518,212.
Application 18/518,212 is a continuation of application No. 18/316,959, filed on May 12, 2023.
Claims priority of provisional application 63/478,472, filed on Jan. 4, 2023.
Claims priority of provisional application 63/341,665, filed on May 13, 2022.
Prior Publication US 2024/0091381 A1, Mar. 21, 2024
Int. Cl. C12N 15/85 (2006.01); A61K 48/00 (2006.01); C07K 14/705 (2006.01); C12N 9/22 (2006.01); C12N 15/11 (2006.01); C12N 15/86 (2006.01); C12N 15/90 (2006.01)
CPC C12N 15/85 (2013.01) [A61K 48/005 (2013.01); C07K 14/705 (2013.01); C12N 9/22 (2013.01); C12N 15/11 (2013.01); C12N 15/86 (2013.01); C12N 15/907 (2013.01); C12N 2310/20 (2017.05); C12N 2320/33 (2013.01); C12N 2750/14143 (2013.01); C12N 2750/14145 (2013.01); C12N 2750/14171 (2013.01); C12N 2830/42 (2013.01)] 20 Claims
 
1. A nucleic acid trans-splicing molecule comprising:
(a) a coding domain sequence (CDS) comprising at least one ABCA4 exon having at least one nucleotide variation relative to a wild-type sequence of the ABCA4 exon at a cryptic splice site within the ABCA4 exon, wherein the at least one nucleotide variation comprises a synonymous nucleotide substitution at a branchpoint of the cryptic splice site or splice site of the cryptic splice site, or comprises synonymous nucleotide substitutions at both a branchpoint of the cryptic splice site and a splice site of the cryptic splice site, wherein the amino acid sequence encoded by the ABCA4 exon is not altered by the synonymous nucleotide substitution or substitutions;
(b) a binding domain that is complementary to a binding site within an endogenous ABCA4 pre-mRNA; and
(c) a splicing domain.