Compositions and methods for epigenetic editing

JP2024501383A5Inactive Publication Date: 2024-12-27CHROMA MEDICINE INC
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Patent Information

Application Number
JP2023563911
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2021-11-17
Filing Date
2021-12-22
Publication Date
2024-12-27
Estimated Expiration
Not applicable · inactive patent

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【0032】本発明の新規な特性は、添付の特許請求の範囲に詳細に記載されている。本発明の特性および利点のより良好な理解は、例示的な実施形態について記載し、本発明の原理が用いられている、以下の詳細な説明、ならびに添付の図面(drawing)(本明細書における「図(FIGURE.)または「図(FIGURES.)」)を参照することによって得られるであろう。

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Abstract

Disclosed herein are compositions and methods comprising epigenetic editors for epigenetic editing, or cells, nucleic acids, and vectors comprising the same. Also disclosed are epigenetically modified chromosomes.
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Claims

1. 1. An epigenetic editor comprising a fusion protein, the fusion protein comprising: (a) a DNA-binding domain; (b) a repressor domain; and (c) a first catalytic domain selected from the group consisting of a DNMT3A catalytic domain and a DNMT3L catalytic domain; (d) a second catalytic domain selected from the group consisting of a DNMT3A catalytic domain and a DNMT3L catalytic domain; Including, the first catalytic domain has fewer than 380 amino acids; or the second catalytic domain has fewer than 380 amino acids; Epigenetic editor.

2. The epigenetic editor of claim 1 , wherein the DNA binding domain binds to a target sequence within a target chromosome that contains a target gene.

3. 3. The epigenetic editor of claim 1 or 2, wherein the repressor domain specifically binds to an epigenetic effector protein in a cell containing a target gene and guides the epigenetic editor to the target gene to effect an epigenetic modification at a nucleotide within the target gene or at a histone bound to the target gene.

4. The repressor domain is ZIM3, ZNF436, ZNF257, ZNF675, ZNF490, ZNF320, ZNF331, ZNF816, ZNF680, ZNF41, ZNF189, ZNF528, ZNF543, ZNF554, ZNF140, ZNF610, ZNF264, ZNF350, ZNF8, ZNF582, ZNF30, ZNF324, ZNF98, ZNF669, ZNF677, ZNF596, ZNF214, ZNF37A, ZNF34, ZNF250, ZNF547, ZNF273, ZNF354A, ZFP82, ZNF224, ZNF33A, ZNF45, ZNF175, ZNF595, ZNF184, ZNF419, ZFP28-1, ZFP28-2, ZNF18, ZNF213, ZNF394, ZFP1, ZFP14, ZNF416, ZNF557, ZNF566, ZNF729, ZIM2, ZNF254, ZNF764, ZNF785, ZNF10, CBX5, RYBP, YAF2, MGA, CBX1, SCMH1, MPP8, SUMO3, HERC2, BIN1, PCGF2, TOX, FOXA1, FOXA2, IRF2BP1, IRF2BP2, IRF2BPL IRF-2BP1_2 N-terminal domain, HOXA13, HOXB13, HOXC13, HOXA11, HOXC11, HOXC10, HOXA10, HOXB9, HOXA9, ZFP28, ZN334, ZN568, ZN37A, ZN181, ZN510, ZN862, ZN140, ZN208, ZN248, ZN571, ZN699, ZN726, ZIK1, ZNF2, Z705F, ZNF14, ZN471, ZN624, ZNF84, ZNF7, ZN891, ZN337, Z705G, ZN529, ZN729, ZN419, Z705A, ZNF45, ZN302, ZN486, ZN621, ZN688, ZN33A, ZN554, ZN878, ZN772, ZN224, ZN184, ZN544, ZNF57, ZN283, ZN549, ZN211, ZN615, ZN253, ZN226, ZN730, Z585A, ZN732, ZN681, ZN667, ZN649, ZN470, ZN484, ZN431, ZN382, ZN254, ZN124, ZN607, ZN317, ZN620, ZN141, ZN584, ZN540, ZN75D, ZN555, ZN658, ZN684, RBAK, ZN829,ZN582、ZN112、ZN716、HKR1、ZN350、ZN480、ZN416、ZNF92、ZN100、ZN736、ZNF74、CBX1、ZN443、ZN195、ZN530、ZN782、ZN791、ZN331、Z354C、ZN157、ZN727、ZN550、ZN793、ZN235、ZNF8、ZN724、ZN573、ZN577、ZN789、ZN718、ZN300、ZN383、ZN429、ZN677、ZN850、ZN454、ZN257、ZN264、ZFP82、ZFP14、ZN485、ZN737、ZNF44、ZN596、ZN565、ZN543、ZFP69、SUMO1、ZNF12、ZN169、ZN433、SUMO3、ZNF98、ZN175、ZN347、ZNF25、ZN519、Z585B、ZIM3、ZN517、ZN846、ZN230、ZNF66、ZFP1、ZN713、ZN816、ZN426、ZN674、ZN627、ZNF20、Z587B、ZN316、ZN233、ZN611、ZN556、ZN234、ZN560、ZNF77、ZN682、ZN614、ZN785、ZN445、ZFP30、ZN225、ZN551、ZN610、ZN528、ZN284、ZN418、MPP8、ZN490、ZN805、Z780B、ZN763、ZN285、ZNF85、ZN223、ZNF90、ZN557、ZN425、ZN229、ZN606、ZN155、ZN222、ZN442、ZNF91、ZN135、ZN778、RYBP、ZN534、ZN586、ZN567、ZN440、ZN583、ZN441、ZNF43、CBX5、ZN589、ZNF10、ZN563、ZN561、ZN136、ZN630、ZN527、ZN333、Z324B、ZN786、ZN709、ZN792、ZN599、ZN613、ZF69B、ZN799、ZN569、ZN564、ZN546、ZFP92、YAF2、ZN723、ZNF34、ZN439、ZFP57、ZNF19、ZN404、ZN274、CBX3、ZNF30、ZN250、ZN570、ZN675、ZN695、ZN548、ZN132、ZN738、ZN420、ZN626、ZN559、ZN460、ZN268、ZN304、ZIM2、ZN605、ZN844、SUMO5、ZN101、ZN783、ZN417、ZN182、ZN823、ZN177、ZN197、ZN717、ZN669、ZN256、ZN251、CBX4、PCGF2、CDY2、CDYL2、HERC2、ZN562、ZN461、Z324A、ZN766、ID2、TOX、ZN274、SCMH1、ZN214、CBX7、ID1、CREM、SCX、ASCL1、ZN764、SCML2、TWST1、CREB1、TERF1、ID3、CBX8、CBX4、GSX1、NKX22、ATF1、TWST2、ZNF17、TOX3、TOX4、ZMYM3、I2BP1、RHXF1、SSX2、I2BPL、ZN680、CBX1、TRI68、HXA13、PHC3、TCF24、CBX3、HXB13、HEY1、PHC2、ZNF81、FIGLA、SAM11、KMT2B、HEY2、JDP2、HXC13、ASCL4、HHEX、HERC2、GSX2、BIN1、ETV7、ASCL3、PHC1、OTP、I2BP2、VGLL2、HXA11、PDLI4、ASCL2、CDX4、ZN860、LMBL4、PDIP3、NKX25、CEBPB、ISL1、CDX2、PROP1、SIN3B、SMBT1、HXC11、HXC10、PRS6A、VSX1、NKX23、MTG16、HMX3、HMX1、KIF22、CSTF2、CEBPE、DLX2、ZMYM3、PPARG、PRIC1、UNC4、BARX2、ALX3、TCF15、TERA、VSX2、HXD12、CDX1、TCF23、ALX1、HXA10、RX、CXXC5、SCML1、NFIL3、DLX6、MTG8、CBX8、CEBPD、SEC13、FIP1、ALX4、LHX3、PRIC2、MAGI3、NELL1、PRRX1、MTG8R、RAX2、DLX3、DLX1、NKX26、NAB1、SAMD7、PITX3、WDR5、MEOX2、NAB2、DHX8、FOXA2、CBX6、EMX2、CPSF6、HXC12、KDM4B、LMBL3、PHX2A、EMX1、NC2B、DLX4、SRY、ZN777、NELL1、ZN398、GATA3、BSH、SF3B4、TEAD1、TEAD3、RGAP1、PHF1、FOXA1、GATA2、FOXO3、ZN212、IRX4、ZBED6、LHX4、SIN3A、RBBP7、NKX61、TRI68、R51A1、MB3L1、DLX5、NOTC1、TERF2, ZN282, RGS12, ZN840, SPI2B, PAX7, NKX62, ASXL2, FOXO1, GATA3, GATA1, ZMYM5, ZN783, SPI2B, LRP1, MIXL1, SGT1, LMCD1, CEBPA, GATA2, SOX14, WTIP, PRP19, CBX6, NKX11, RBBP4, DMRT2, SMCA2, and fragments thereof; The epigenetic editor of any one of claims 1 to 3, selected from the group consisting of:

5. The epigenetic editor of any one of claims 1 to 4, wherein the repressor domain is selected from the group consisting of SEQ ID NOs: 67 to 595.

6. The epigenetic editor of claim 4, wherein the repressor domain is selected from the group consisting of ZIM3, ZNF264, ZN577, ZN793, ZFP28, ZN627, RYBP, TOX, TOX3, TOX4, I2BP1, SCMH1, SCML2, CDYL2, CBX8, CBX5, CBX1, and fragments thereof.

7. The epigenetic editor of any one of claims 1 to 6, wherein the DNA binding domain comprises a zinc finger motif or a zinc finger array.

8. The epigenetic editor of any one of claims 1 to 6, wherein the DNA binding domain comprises a nucleic acid-guided DNA binding domain bound to a guide polynucleotide.

9. The epigenetic editor of claim 8, wherein the DNA binding domain comprises a CRISPR-Cas protein bound to the guide polynucleotide.

10. The epigenetic editor of claim 8 or 9, wherein the guide polynucleotide hybridizes to a target sequence.

11. The epigenetic editor of claim 9 or 10, wherein the CRISPR-Cas protein comprises a nuclease-inactive Cas9 (dCas9), and the dCas9 is dSpCas9.

12. An epigenetic editor described in any one of claims 1 to 11, wherein the first catalytic domain is a DNMT3A catalytic domain.

13. An epigenetic editor described in any one of claims 1 to 12, wherein the second catalytic domain is a DNMT3L catalytic domain.

14. An epigenetic editor described in any one of claims 1 to 13, wherein the fusion protein comprises, from N-terminus to C-terminus, a DNMT3A catalytic domain, a DNMT3L catalytic domain, the DNA binding domain, and the repressor domain.

15. An epigenetic editor described in any one of claims 1 to 14, wherein the first catalytic domain or the second catalytic domain is selected from the group consisting of SEQ ID NOs: 33, 34, 37, 38, 39 and 40.