IP Library › Granted Patent US 12686869
Granted Patent B1
US 12686869 · App. 19/457,807 · Granted Jul 21, 2026

Methods and compositions for trans-splicing utilizing trifunctional elements

Inventors: Jacob Borrajo (San Francisco, CA); Brigit Riley (San Francisco, CA); Kamyab Javanmardi (San Francisco, CA); Patricia Biezonski (San Francisco, CA); Samuel Demario (San Francisco, CA)
Assignee: Amber Bio Inc.
C12N15/1136C12N2310/14C12N2320/33
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Quick Facts
Patent No.
US 12686869
App. No.
19/457,807
Granted
Jul 21, 2026
Kind
B1
Abstract

The present disclosure provides a trans-splicing molecule that has a trifunctional element suitable for targeted trans-splicing of an RNA or pre-mRNA molecule.

Claims (48)

1 . A trans-splicing molecule comprising a trifunctional element suitable for targeted trans-splicing of an RNA or pre-mRNA molecule, comprising:

(i) one or more stabilizing structural elements having at least 95% sequence identity to SEQ ID NO: 216 or 274;

(ii) one or more cleavage elements having at least 95% sequence identity to SEQ ID NO: 217; and

(iii) a termination sequence having at least 95% sequence identity to SEQ ID NO: 218.

2 . The trans-splicing molecule of claim 1 , comprising:

(i) one or more stabilizing structural elements having at least 95% sequence identity to SEQ ID NO: 216;

(ii) one or more cleavage elements having at least 95% sequence identity to SEQ ID NO: 217; and

(iii) a termination sequence having at least 95% sequence identity to SEQ ID NO: 218.

3 . The trans-splicing molecule of claim 1 , comprising:

(i) one or more stabilizing structural elements having at least 98% sequence identity to SEQ ID NO: 216 or 274;

(ii) one or more cleavage elements having at least 98% sequence identity to SEQ ID NO: 217; and

(iii) a termination sequence having at least 98% sequence identity to SEQ ID NO: 218.

4 . The trans-splicing molecule of claim 1 , comprising:

(i) one or more stabilizing structural elements having at least 99% sequence identity to SEQ ID NO: 216 or 274;

(ii) one or more cleavage elements having at least 99% sequence identity to SEQ ID NO: 217; and

(iii) a termination sequence having at least 99% sequence identity to SEQ ID NO: 218.

5 . The trans-splicing molecule of claim 1 , further comprising one or more complementary regions (CR) having at least 98% sequence identity to one of SEQ ID NOs: 212-214.

6 . The trans-splicing molecule of claim 5 , wherein the one or more CRs are located outside of the one or more stabilizing structural elements.

7 . The trans-splicing molecule of claim 5 , wherein the one or more CRs are located inside the one or more stabilizing structural elements.

8 . The trans-splicing molecule of claim 1 , further comprising a splice acceptor (SA) or splice donor (SD) of one of:

i. CAGGTAAGT;

ii. CAGGTAAGA;

iii. CAGGTGAGT;

iv. CAGGTAGGT; and

v. CAGGTAAGG.

9 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises a CMV enhancer having at least 98% sequence identity to SEQ ID NO: 204.

10 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises a CMV promoter having at least 98% sequence identity to SEQ ID NO: 205.

11 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises an untranscribed region having at least 98% sequence identity to SEQ ID NO: 206.

12 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises an Usherin 5′ UTR sequence having at least 98% sequence identity to SEQ ID NO: 207 or SEQ ID NO: 208.

13 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises an Usherin coding sequence having at least 98% sequence identity to SEQ ID NO: 209.

14 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises a splice donor (SD) sequence of: GTAAGT.

15 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises a scaffold sequence having at least 98% sequence identity to SEQ ID NO: 211.

16 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises a filler sequence having at least 98% sequence identity to SEQ ID NO: 215.

17 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises a stabilizing structural element sequence having at least 98% sequence identity to SEQ ID NO: 216 or SEQ ID NO: 274.

18 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises a cleavage element sequence having at least 98% sequence identity to SEQ ID NO: 217.

19 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule further comprises a termination sequence having at least 98% sequence identity to SEQ ID NO: 218.

20 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule has at least 95% identity to one of SEQ ID NOs: 255-258.

21 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule has at least 98% identity to one of SEQ ID NOs: 255-258.

22 . The trans-splicing molecule of claim 1 , wherein the trans-splicing molecule has at least 99% identity to one of SEQ ID NOs: 255-258.

23 . A trans-splicing molecule comprising a trifunctional element suitable for targeted trans-splicing of an RNA or pre-mRNA molecule, comprising:

(i) one or more stabilizing structural elements,

(ii) one or more cleavage elements, and

(iii) a termination sequence,

wherein the trans-splicing molecule has at least 99% identity to one of SEQ ID NOs: 255-258.

24 . The trans-splicing molecule of claim 23 , wherein the trans-splicing molecule has at least 99% identity to SEQ ID NO: 255.

25 . The trans-splicing molecule of claim 23 , wherein the trans-splicing molecule has at least 99% identity to SEQ ID NO: 256.

26 . The trans-splicing molecule of claim 23 , wherein the trans-splicing molecule has at least 99% identity to SEQ ID NO: 257.

27 . The trans-splicing molecule of claim 23 , wherein the trans-splicing molecule has at least 99% identity to SEQ ID NO: 258.