US 12,442,003 B2
Trans-splicing molecules
Philip R. Johnson, Bryn Mawr, PA (US); Bruce C. Schnepp, Havertown, PA (US); Jean Bennett, Bryn Mawr, PA (US); Scott J. Dooley, Clementon, NJ (US); Krishna Jawaharlal Fisher, Durham, NC (US); and Junwei Sun, Philadelphia, PA (US)
Assigned to Ascidian Therapeutics, Inc., Boston, MA (US); and The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
Filed by Ascidian Therapeutics, Inc., Boston, MA (US); and The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
Filed on May 24, 2024, as Appl. No. 18/673,713.
Application 18/673,713 is a continuation of application No. 17/047,496, granted, now 11,993,776, previously published as PCT/US2019/027981, filed on Apr. 17, 2019.
Claims priority of provisional application 62/658,658, filed on Apr. 17, 2018.
Claims priority of provisional application 62/658,667, filed on Apr. 17, 2018.
Prior Publication US 2024/0318186 A1, Sep. 26, 2024
Int. Cl. C12N 15/113 (2010.01); C07K 14/705 (2006.01)
CPC C12N 15/1138 (2013.01) [C07K 14/705 (2013.01); C07K 2319/71 (2013.01); C07K 2319/85 (2013.01); C12N 2320/33 (2013.01); C12N 2320/34 (2013.01)] 21 Claims
 
1. A nucleic acid trans-splicing molecule comprising, operatively linked in a 5′-to-3′ direction:
(a) a binding domain, wherein the binding domain comprises a sequence ranging from 50-300 nucleotides in length and is configured to bind ABCA4 intron 22 at a binding site within nucleotides 60 to 570, 600 to 800, or 900 to 1,350 of SEQ ID NO: 28;
(b) a splicing domain configured to mediate trans-splicing; and
(c) a coding domain comprising functional ABCA4 exons 23-50;
wherein the nucleic acid trans-splicing molecule is configured to trans-splice the coding domain to endogenous ABCA4 exon 22, thereby replacing endogenous ABCA4 exons 23-50 with the functional ABCA4 exons 23-50.