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US 2025/0051780 A1Published application
COMPOSITIONS AND METHODS FOR MODULATING mRNA SPLICING
AssigneeEntrada Therapeutics, Inc.
InventorsZiqing QIAN, Natarajan SETHURAMAN, Xiulong SHEN, Haoming LIU, Xiang LI
Life of this patent
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Abstract
Compounds include at least one cyclic cell penetrating peptide (cCPP) conjugated to an antisense compound (AC). The AC modulates splicing of an RNA transcript. For example, the AC induces exon skipping. Exon skipping can result in down-regulation of expression or activity of a protein. Exon skipping may cause a frameshift in a resulting mRNA. The frameshift may result in a premature termination codon. The frameshift may result in nonsense mediated decay.
Claims22
1-134. (canceled)
A compound comprising:
- (a) a cyclic cell penetrating peptide of the formula:
- or a protonated form or salt thereof, wherein:
- R1, R2, and R3 are each independently H or an aromatic or heteroaromatic side chain of an amino acid;
- at least two of R1, R2, and R3 are the side chain of phenylalanine;
- R4 and R7 are independently H or an amino acid side chain;
- each m is independently an integer from 0 to 3;
- AAsc is an amino acid side chain;
- and
- q is 1, 2, 3, or 4;
- (b) an exocyclic peptide comprising from 2 to 10 amino acid residues, wherein 2, 3, or 4 of the residues are lysine residues;
- (c) a linker of formula:
- wherein:
- x′ is an integer from 1-23;
- y is an integer from 1-5;
- z′ is an integer from 1-23;
- * is the point of attachment to the AASC of the cyclic peptide;
- and M is a bonding group;
- and
- (d) an antisense compound (AC) comprising a nucleotide sequence that is complementary to a target nucleotide sequence of a target transcript of a target gene, wherein the AC specifically hybridizes to the target nucleotide sequence and modulates splicing of the target transcript to downregulate expression or activity of a protein expressed from the target transcript.
16 more elements
Dependencies are inferred from the claim text.