IP Library Granted Patent US 12,560,608
Granted Patent B2
US 12,560,608 · App. 18/491,255 · Granted Feb 24, 2026

Detection of molecular associations

Inventors: Mitchell Guttman (Los Angeles, CA); Mario R. Blanco (Los Angeles, CA); Ward Walkup, IV (Lincoln, MA)
Assignee: California Institute of Technology
G01N33/573C12N15/907C12Y201/01043
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,560,608
App. No.
18/491,255
Granted
Feb 24, 2026
Kind
B2
Abstract

In some embodiments, methods of detecting an association between a query protein and a target moiety are described. In some embodiments, compositions are described. In some embodiments, kits are described.

Claims (48)

1 . A kit comprising:

a. a vector comprising 1) an insertion site, 2) a tag coding sequence, and 3) a counterpart polypeptide coding sequence; wherein

the insertion site is arranged to place a query protein coding sequence in frame with the tag coding sequence without any intervening stop codon,

wherein

upon the insertion of the query protein coding sequence in the insertion site the vector encodes a tagged query protein with the counterpart polypeptide sequence located at the N-terminal region of the query protein;

b. a covalent polypeptide tag, wherein the covalent polypeptide tag and the counterpart polypeptide sequence are configured to specifically covalently bind to each other;

c. a substrate configured to specifically bind covalently to the encoded tag, and

d. a crosslinking agent.

2 . The kit of claim 1 , further comprising a barcode.

3 . The kit of claim 2 , wherein the barcode comprises a coding sequence of the query protein fused to the covalent polypeptide tag.

4 . The kit of claim 1 , wherein the covalent polypeptide tag and counterpart polypeptide sequence comprise a Spytag and SpyCatcher; or Isopeptag and pilin-C; or SnoopTag and SnoopCatcher; or DogTag and SnoopTagJr; or a SdyTag and SdyCatcher.

5 . The kit of claim 1 , wherein

the tag coding sequence encodes a haloalkane dehalogenase and the substrate comprises a haloalkane resin; or

the tag coding sequence enocodes a DNA methyltransferase and the substrate comprises a benzylguanine resin; or

the tag coding sequence enocodes a DNA methyltransferase and the substrate comprises a benzylcytosine resin; or

the tag coding sequence enocodes an isopeptag and the substrate comprises a pilin-C protein; or

the tag coding sequence enocodes a SpyTag, and the substrate comprises a SpyCatcher protein; or

the tag coding sequence enocodes SnoopTag and the substrate comprises a SnoopCatcher protein; or

the tag coding sequence enocodes DogTag and the substrate comprises SnoopTagJr; or

the tag coding sequence enocodes SdyTag and the substrate comprises SdyCatcher; or

the tag coding sequence enocodes Cpe0147565-587 and the substrate comprises Cpe0147439-563.

6 . The kit of claim 1 , wherein the crosslinking agent comprises an amine-to-amine crosslinker, disuccinimidyl suberate, disuccinimidyl tartrate, a sulfhydryl-to-sulfhydryl crosslinker, bis-maleimidoethane or dithio-bis-maleimidoethane, an aryl-azide, N-5-Azido-2-nitrobenzyloxysuccinimide, sulfosuccinimidyl 6-(4′-azido-2′-nitrophenylamino)hexanoate), a diazirine, succinimidyl 4,4′-azipentanoate, an NHS ester, an imidoester, a difluoro group, an NHS-haloacetyl group, an NHS-maleimide group, an NHS-pyridyldithiol group, a carbodiimide ester and NHS ester, a malemide and a hydrazine group, a pyridyldithiol and a hydrazine group, a NHS ester and an aryl azide, a NHS ester and a diazirine, a NHS ester and an aryl azide, or ultraviolet radiation.

7 . The kit of claim 1 , wherein the substrate comprises a magnetic bead.

8 . The kit of claim 1 , wherein the substrate does not comprise an immunoglobulin or binding fragment thereof.

9 . A composition comprising:

a vector comprising an insertion site, a tag coding sequence, and a counterpart polypeptide coding sequence, wherein

the insertion site is arranged to place a query protein coding sequence in frame with the tag coding sequence without any intervening stop codon, wherein

upon the insertion of the query protein coding sequence in the insertion site the vector encodes a tagged query protein with the counterpart polypeptide sequence located at the N-terminal region of the query protein;

and a covalent polypeptide tag, wherein

the covalent polypeptide tag and the counterpart polypeptide sequence are configured to specifically covalently bind to each other.

10 . The composition of claim 9 , wherein the covalent polypeptide tag is fused to a polynucleotide comprising a coding sequence of the query protein.

11 . The composition of claim 9 , wherein the covalent polypeptide tag and counterpart polypeptide sequence comprise a Spytag and SpyCatcher; or Isopeptag and pilin-C; or SnoopTag and SnoopCatcher; or DogTag and SnoopTagJr; or SdyTag and SdyCatcher.

12 . The composition of claim 9 , further comprising a substrate configured to specifically bind covalently to the encoded tag.

13 . The composition of claim 12 , wherein:

the tag coding sequence enocodes a haloalkane dehalogenase and the substrate comprises a haloalkane resin; or

the tag coding sequence enocodes a DNA methyltransferase and the substrate comprises a benzylguanine resin; or

the tag coding sequence enocodes a DNA methyltransferase and the substrate comprises a benzylcytosine resin; or

the tag coding sequence enocodes an isopeptag and the substrate comprises a pilin-C protein; or

the tag coding sequence enocodes a SpyTag, and the substrate comprises a SpyCatcher protein; or

the tag coding sequence enocodes SnoopTag and the substrate comprises a SnoopCatcher protein; or

the tag coding sequence enocodes DogTag and the substrate comprises SnoopTagJr, or

the tag coding sequence enocodes SdyTag and the substrate comprises SdyCatcher; or

the tag coding sequence enocodes Cpe0147565-587 and the substrate comprises Cpe0147439-563.

14 . The composition of claim 12 , wherein the substrate comprises a magnetic bead.

15 . The composition of claim 12 , wherein the substrate does not comprise an immunoglobulin or binding fragment thereof.

16 . The composition of claim 9 , further comprising a crosslinking agent.

17 . The composition of claim 16 , wherein the crosslinking agent comprises an amine-to-amine crosslinker, disuccinimidyl suberate, disuccinimidyl tartrate, a sulfhydryl-to-sulfhydryl crosslinker, bis-maleimidoethane or dithio-bis-maleimidoethane, an aryl-azide, N-5-Azido-2-nitrobenzyloxysuccinimide, sulfosuccinimidyl 6-(4′-azido-2′-nitrophenylamino)hexanoate), a diazirine, succinimidyl 4,4′-azipentanoate, an NHS ester, an imidoester, a difluoro group, an NHS-haloacetyl group, an NHS-maleimide group, an NHS-pyridyldithiol group, a carbodiimide ester and NHS ester, a malemide and a hydrazine group, a pyridyldithiol and a hydrazine group, a NHS ester and an aryl azide, a NHS ester and a diazirine, a NHS ester and an aryl azide, and ultraviolet radiation.

18 . The composition of claim 9 , wherein the composition is under denaturing conditions.

Assignments (4)
CONFIRMATORY LICENSE Recorded Jan 29, 2024
From: CALIFORNIA INSTITUTE OF TECHNOLOGY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 066277/0871 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 6, 2023
From: GUTTMAN, MITCHELL
To: CALIFORNIA INSTITUTE OF TECHNOLOGY; HERITAGE MEDICAL RESEARCH INSTITUTE
Reel/Frame 065466/0064 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 6, 2023
From: BLANCO, MARIO R.; WALKUP, WARD, IV
To: CALIFORNIA INSTITUTE OF TECHNOLOGY
Reel/Frame 065466/0777 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 6, 2023
From: HERITAGE MEDICAL RESEARCH INSTITUTE
To: CALIFORNIA INSTITUTE OF TECHNOLOGY
Reel/Frame 065466/0832 →
Continuity (3)
Division 16573673 · Sep 17, 2019
Provisional Application 62732413 · Sep 17, 2018
Related Publication 20240125783A1 · Apr 18, 2024
References Cited (144)
US 7238478B2 · Braman et al. · 2007 [cited by applicant]
US 11078480B2 · Guttman et al. · 2021 [cited by applicant]
US 11634752B2 · Nolan · 2023 [cited by applicant]
US 11828684B2 · Guttman et al. · 2023 [cited by applicant]
US 20100099200A1 · Nazabal et al. · 2010 [cited by applicant]
US 20130021725A1 · Huang · 2013 [cited by applicant]
US 20130212725A1 · Kühn et al. · 2013 [cited by applicant]
US 20150225786A1 · Litterst et al. · 2015 [cited by applicant]
US 20160194699A1 · Borodina et al. · 2016 [cited by applicant]
US 20180320175A1 · Lee et al. · 2018 [cited by applicant]
US 20190145982A1 · Chee et al. · 2019 [cited by applicant]
US 20190187156A1 · Quinodoz et al. · 2019 [cited by applicant]
US 20200157153A1 · Schmidt-Dannert et al. · 2020 [cited by applicant]
US 20240384325A1 · Wolin et al. · 2024 [cited by applicant]
WO WO2003089900A2 · 2003 [cited by applicant]
WO 2012041802A1 · 2012 [cited by applicant]
WO 2012071428A2 · 2012 [cited by applicant]
WO 2012106385A2 · 2012 [cited by applicant]
WO WO2017192633A1 · 2017 [cited by applicant]
WO 2020061036A1 · 2020 [cited by applicant]
WO 2020061262A1 · 2020 [cited by applicant]
WO 2022173690A1 · 2022 [cited by applicant]
WO 2023023584A2 · 2023 [cited by applicant]
Bantignies, F. et al. Polycomb-Dependent Regulatory Contacts between Distant Hox Loci in Drosophila. Cell 144, 214-226 (2011). [cited by applicant]
Beltran, M. et al. The interaction of PRC2 with RNA or chromatin is mutually antagonistic. Genome Res. 26, 896-907 (2016). [cited by applicant]
Blackstock, D. et al., Halo-tag mediated self-labeling of fluorescent proteins to molecular beacons for nucleic acid detection, ChemCommun. 2014, vol. 50, pp. 13735-13738. [cited by applicant]
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114-2120 (2014). [cited by applicant]
Brockdorff, N. Noncoding RNA and Polycomb recruitment. RNA 19, 429-442 (2013). [cited by applicant]
Castello “Identification of RNA-binding domains of RNA-binding proteins in cultured cells on a system-wide scale with RBDmap” (Nature Protocols 2017 12:2447-2464). (Year: 2017). [cited by applicant]
Castello, A. et al. Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 149, 1393-1406 (2012). [cited by applicant]
Castello, A., Hentze, M. W. & Preiss, T. Metabolic Enzymes Enjoying New Partnerships as RNA-Binding Proteins. Trends Endocrinol. Metab. 26, 746-57 (2015). [cited by applicant]
Cerase, A. et al. Spatial separation of Xist RNA and polycomb proteins revealed by superresolution microscopy. Proc Natl Acad Sci U S A 111, 2235-2240 (2014). [cited by applicant]
Chen, C.-K. et al. Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing. Science (80-. ). 354, (2016). [cited by applicant]
Cheutin, T. & Cavalli, G. Polycomb silencing: from linear chromatin domains to 3D chromosome folding. Curr Opin Genet Dev 25C, 30-37 (2014). [cited by applicant]
Chu, C. et al. Systematic discovery of Xist RNA binding proteins. Cell 161, 404-416 (2015). [cited by applicant]
Cifuentes-Rojas, C., Hernandez, A. J., Sarma, K. & Lee, J. T. Regulatory Interactions between RNA and Polycomb Repressive Complex 2. Mol Cell 55, 171-185 (2014). [cited by applicant]
Cirillo, D. et al. Quantitative predictions of protein interactions with long noncoding RNAs. Nat. Methods 14, 5-6 (2016). [cited by applicant]
Da Rocha, S. T. et al. Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome. Mol Cell 53, 301-316 (2014). [cited by applicant]
Darnell, R. B. Hits-Clip: panoramic views of protein-RNA regulation in living cells. Wiley Interdiscip Rev RNA 1, 266-286 (2010). [cited by applicant]
Davidovich, C. et al. Toward a Consensus on the Binding Specificity and Promiscuity of PRC2 for RNA. Mol Cell 57, 552-558 (2015). [cited by applicant]
Davidovich, C., Zheng, L., Goodrich, K. J. & Cech, T. R. Promiscuous RNA binding by Polycomb repressive complex 2. Nat Struct Mol Biol 20, 1250-1257 (2013). [cited by applicant]
Derrien, T. et al. The GENCODE v7 catalog of human long noncoding RNAs: analysis of their gene structure, evolution, and expression. Genome Res 22, 1775-1789 (2012). [cited by applicant]
Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15-21 (2013). [cited by applicant]
Engreitz, Jesse M. et al.; “The Xist IncRNA exploits three-dimensional genome architecture to spread across the X-chromosome”; Science; Aug. 16, 2013; 341(6147); 18pp.; doi:10.1126/science.1237973. [cited by applicant]
Froberg, J. E., Yang, L. & Lee, J. T. Guided by RNAs: X-Inactivation as a Model for IncRNA Function. J. Mol. Biol. 425, 3698-3706 (2013). [cited by applicant]
G Hendrickson, D., Kelley, D. R., Tenen, D., Bernstein, B. & Rinn, J. L. Widespread RNA binding by chromatin-associated proteins. Genome Biol. 17, 28 (2016). [cited by applicant]
Galupa, R. & Heard, E. X-chromosome inactivation: new insights into cis and trans regulation. Curr. Opin. Genet. Dev. 31, 57-66 (2015). [cited by applicant]
Guttman, M. & Rinn, J. L. Modular regulatory principles of large non-coding RNAs. Nature 482, (2012). [cited by applicant]
Guttman, M. et al. lincRNAs act in the circuitry controlling pluripotency and differentiation. Nature 477, 295-300 (2011). [cited by applicant]
Hafner, M. et al. Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell 141, 129-141 (2010). [cited by applicant]
Huarte, M. et al. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell 142, 409-419 (2010). [cited by applicant]
International Search Report and Written Opinion in Application No. PCT/US2019/051500, Nov. 19, 2019. [cited by applicant]
Kalantry, S. & Magnuson, T. The Polycomb group protein EED is dispensable for the initiation of random X-chromosome inactivation. PLoS Genet 2, e66 (2006). [cited by applicant]
Kaneko, S. et al. Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Mol Cell 53, 290-300 (2014). [cited by applicant]
Kaneko, S. et al. Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA. Genes Dev. 24, 2615-20 (2010). [cited by applicant]
Kaneko, S., Son, J., Shen, S. S., Reinberg, D. & Bonasio, R. PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells. Nat Struct Mol Biol 20, 1258-1264 (2013). [cited by applicant]
Kanhere, A. et al. Short RNAs are transcribed from repressed polycomb target genes and interact with polycomb repressive complex-2. Mol. Cell 38, 675-88 (2010). [cited by applicant]
Keene, J. D., Komisarow, J. M. & Friedersdorf, M. B. RIP-Chip: the isolation and identification of mRNAs, microRNAs and protein components of ribonucleoprotein complexes from cell extracts. Nat. Protoc. 1, 302-307 (2006… [cited by applicant]
Khalil, A. M. et al. Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression. Proc Natl Acad Sci U S A 106, 11667-11672 (2009). [cited by applicant]
Kohlmaier, A. et al. A chromosomal memory triggered by Xist regulates histone methylation in X inactivation. PLoS Biol. 2, E171 (2004). [cited by applicant]
Konig, J. et al. iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat Struct Mol Biol 17, 909-915 (2010). [cited by applicant]
Koziol, M. J. & Rinn, J. L. RNA traffic control of chromatin complexes. Curr. Opin. Genet. Dev. 20, 142-8 (2010). [cited by applicant]
Kozlov, I.A. et al., Efficient Strategies for the Conjugation of Oligonucleotides to Antibodies Enabling Highly Sensitive Protein Detection, Wiley InterScience, Mar. 8, 2004, pp. 621-630. [cited by applicant]
Kundu, S. et al. Polycomb Repressive Complex 1 Generates Discrete Compacted Domains that Change during Differentiation. Mol. Cell 65, 432-446.e5 (2017). [cited by applicant]
Kwon, S. C. et al. The RNA-binding protein repertoire of embryonic stem cells. Nat Struct Mol Biol 20, 1122-1130 (2013). [cited by applicant]
Lassmann, T., Hayashizaki, Y. & Daub, C. O. TagDust—a program to eliminate artifacts from next generation sequencing data. Bioinformatics 25, 2839-2840 (2009). [cited by applicant]
Lee, J. T. Epigenetic regulation by long noncoding RNAs. Science (80-. ). 338, 1435-1439 (2012). [cited by applicant]
Lee, J. T. Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome. Genes Dev 23, 1831-1842 (2009). [cited by applicant]
Lee, S. et al. Noncoding Rna Norad Regulates Genomic Stability by Sequestering PUMILIO Proteins. Cell 164, 69-80 (2016). [cited by applicant]
Li (J. Mol. Biol. 2014 426: 309-317). (Year: 2014). [cited by applicant]
Licatalosi, D. D. et al. HITS-CLIP yields genome-wide insights intoprocessing. Nature 456, 464-469 (2008). [cited by applicant]
Los, G.V et al., HaloTag: A Novel Protein Labeling Technology for Cell Imaging and Protein Analysis, ACS Chemical Biology, vol. 3, No. 6, Jun. 6, 2008, pp. 373-382. [cited by applicant]
Lu, Z. et al. RNA Duplex Map in Living Cells Reveals Higher-Order Transcriptome Structure. Cell 165, 1267-1279 (2016). [cited by applicant]
Margueron, R. & Reinberg, D. The Polycomb complex PRC2 and its mark in life. Nature 469, 343-349 (2011). [cited by applicant]
Mili, S. & Steitz, J. A. Evidence for reassociation of RNA-binding proteins after cell lysis: implications for the interpretation of immunoprecipitation analyses. RNA 10, 1692-1694 (2004). [cited by applicant]
Minajigi, A. et al. Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science (80-.). 349, (2015). [cited by applicant]
Mohammad, F. et al. Konq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region. Mol. Cell. Biol. 28, 3713-28 (2008). [cited by applicant]
Moindrot, B. et al. A Pooled shRNA Screen Identifies Rbm15, Spen, and Wtap as Factors Required for Xist RNA-Mediated Silencing. Cell Rep. (2015). doi:10.1016/j.celrep.2015.06.053. [cited by applicant]
Monfort, A., Minin, G. Di, Postlmayr, A., Arieti, F. & Wutz, A. Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem. Cell Rep. 1-8 (2015). doi:10.1016… [cited by applicant]
Ozdilek, B. A. et al. Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding. Nucleic Acids Res. (2017). doi:10.1093/nar/gkx460. [cited by applicant]
Pandey, R. R. et al. Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol. Cell 32, 232-46 (2008). [cited by applicant]
Peritz, T. et al. Immunoprecipitation of mRNA-protein complexes. Nat. Protoc. 1, 577-580 (2006). [cited by applicant]
Plath, K. et al. Role of histone H3 lysine 27 methylation in X inactivation. Science (80-.). 300, 131-135 (2003). [cited by applicant]
Portoso, M. et al. PRC2 is dispensable for HOTAIR ?mediated transcriptional repression. EMBO J. 36, 981-994 (2017). [cited by applicant]
Ray, D. et al. Rapid and systematic analysis of the RNA recognition specificities of RNA-binding proteins. Nat. Biotechnol. 27, 667-670 (2009). [cited by applicant]
Rinn, J. L. & Chang, H. Y. Genome regulation by long noncoding RNAs. Annu Rev Biochem 81, 145-166 (2012). [cited by applicant]
Rinn, J. L. et al. Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 129, 1311-1323 (2007). [cited by applicant]
Rosenberg et al., “Denaturing CLIP, dCLIP, Pipeline Identifies Discrete RNA Footprints on Chromatin-Associated Proteins and Reveals that CBX7 Targets 30 UTRs to Regulate mRNA Expression”, Cell Systems 5, 368-385, Oct. 2… [cited by applicant]
Schoeftner, S. et al. Recruitment of PRC1 function at the initiation of X inactivation independent of PRC2 and silencing. EMBO J. 25, 3110-3122 (2006). [cited by applicant]
Shishkin, A. A. et al. Simultaneous generation of many RNA-seq libraries in a single reaction. Nat. Methods 12, 323-5 (2015). [cited by applicant]
Si SpyTag/SpyCatcher Cyclization Enhances the Thermostability of Firefly Luciferase PlosOne 2016 e0162318 (Year: 2016). [cited by applicant]
Simon, J. A. & Kingston, R. E. Mechanisms of polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol 10, 697-708 (2009). [cited by applicant]
Singh, V. et al., Genetically Encoded Multispectral Labeling of Proteins with Polyfluorophores on a DNA Backbone, NIH Public Access Author Manuscript, J. Am. Chem. Soc. 2013, 135(16) 19 pages. [cited by applicant]
Spitale, R. C., Tsai, M.-C. & Chang, H. Y. RNA templating the epigenome: long noncoding RNAs as molecular scaffolds. Epigenetics 6, 539-43 (2011). [cited by applicant]
Sundararaman, B. et al. Resources for the Comprehensive Discovery of Functional RNA Elements. Mol. Cell 61, 903-913 (2016). [cited by applicant]
Terranova, R. et al. Polycomb group proteins Ezh2 and Rnf2 direct genomic contraction and imprinted repression in early mouse embryos. Dev. Cell 15, 668-79 (2008). [cited by applicant]
Tichon, A. et al. A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells. Nat. Commun. 7, 12209 (2016). [cited by applicant]
Tsai, M. C. et al. Long noncoding RNA as modular scaffold of histone modification complexes. Science (80-. ). 329, 689-693 (2010). [cited by applicant]
Ule, J. et al. CLIP Identifies Nova-Regulated RNA Networks in the Brain. Science (80-. ). 302, 1212-1215 (2003). [cited by applicant]
Van Nostrand, E. L. et al. Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat. Methods (2016). doi:10.1038/nmeth.3810. [cited by applicant]
Wang, D. et al. LncRNA MALAT1 enhances oncogenic activities of EZH2 in castration-resistant prostate cancer. Oncotarget 6, 41045-55 (2015). [cited by applicant]
Wang, X. et al. Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines. Mol. Cell 65, 1056-1067.e5 (2017). [cited by applicant]
Woo, C. J. et al. Gene activation of SMN by selective disruption of IncRNA-mediated recruitment of PRC2 for the treatment of spinal muscular atrophy. Proc. Natl. Acad. Sci. U. S. A. 114, E1509-E1518 (2017). [cited by applicant]
Wu, H.-A. & Bernstein, E. Partners in Imprinting: Noncoding RNA and Polycomb Group Proteins. Dev. Cell 15, 637-638 (2008). [cited by applicant]
Wutz, A. Gene silencing in X-chromosome inactivation: advances in understanding facultative heterochromatin formation. Nat. Rev. Genet. 12, 542-553 (2011). [cited by applicant]
Wutz, A., Rasmussen, T. P. & Jaenisch, R. Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nat. Genet. 30, 167-174 (2002). [cited by applicant]
Xu, H et al. FastUniq: A Fast De Novo Duplicates Removal Tool for Paired Short Reads. PLoS One 7, e52249 (2012). [cited by applicant]
Yang, L. et al. ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell 147, 773-788 (2011). [cited by applicant]
Yang, Y. W. et al. Essential role of IncRNA binding for WDR5 maintenance of active chromatin and embryonic stem cell pluripotency. Elife 3, e02046 (2014). [cited by applicant]
Yeo, G. W. et al. An RNA code for the FOX2 splicing regulator revealed by mapping RNA-protein interactions in stem cells. Nat. Struct. Mol. Biol. 16, 130-137 (2009). [cited by applicant]
Zakeri “Peptide tag forming a rapid covalent bound to a protein, through engineering a bacterial adhesion” PNAS 2012 109: E692-E697) (Year: 2012). [cited by applicant]
Zhao, J. et al. Genome-wide identification of polycomb-associated RNAs by RIP-seq. Mol Cell 40, 939-953 (2010). [cited by applicant]
Zhao, J., Sun, B. K., Erwin, J. A., Song, J. J. & Lee, J. T. Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science (80-. ). 322, 750-756 (2008). [cited by applicant]
Zovoilis, A., Cifuentes-Rojas, C., Chu, H.-P., Hernandez, A. J. & Lee, J. T. Destabilization of B2 RNA by EZH2 Activates the Stress Response. Cell 167, 1788-1802.e13 (2016). [cited by applicant]
Barendt, et al., “Streamlined protocol for mRNA display,” ACS Comb. Sci. (2013), doi: 10.1021/co300135r. [cited by applicant]
Buldun et al., Snoopligase Catalyzes Peptide-Peptide Locking and Enables Solid-Phase Conjugate Isolation, Journal of the American Chemical Society, Feb. 8, 2018, 30 pages. [cited by applicant]
C. Keryer-Bibens, C. Barreau, H. B. Osborne, Tethering of proteins to RNAs by bacteriophage proteins. Biol. Cell (2008), doi:10.1042/BC20070067. [cited by applicant]
Chen, C.K. et al., Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing, Science, vol. 354, Issue 6311, Oct. 28, 2016, pp. 468-472. [cited by applicant]
Daniel M. et al., “uvCLAP is a fast and non-radioactive method to identify in vivo targets of RNA-binding proteins”, Nature Communications, vol. 9, No. 1, Mar. 20, 2018. [cited by applicant]
Frei A. P. et al., “Highly multiplexed simultaneous detection of RNAs and proteins in single cells”, Nature Methods, vol. 13, No. 3, Mar. 1, 2016, pp. 269-275. [cited by applicant]
Glen L. et al., “Nucleic Acid-Barcoding Technologies: Converting DNA Sequencing into a Broad-Spectrum Molecular Counter”, Angewandte Chemie International Edition, vol. 58, No. 13, Aug. 28, 2018, pp. 4144-4162. [cited by applicant]
International Preliminary Report on Patentability, re PCT Application No. PCT/US2019/051500, dated Mar. 25, 2021. [cited by applicant]
International Preliminary Report on Patentability, re PCT Application No. PCT/US2019/051842, dated Apr. 1, 2021. [cited by applicant]
International Search Report and Written Opinion, re PCT Application No. PCT/US2019/051842, dated Dec. 18, 2019. [cited by applicant]
International Search Report and Written Opinion, re PCT Application No. PCT/US2024/029518, dated Sep. 9, 2024. [cited by applicant]
Jiaqi G. et al., “GoldCLIP: Gel-omitted Ligation-dependent Clip”, Genomics Proteomics and Bioinformatics, vol. 16, No. 2, Apr. 28, 2018, pp. 136-143. [cited by applicant]
Kozlov, I.A. et al., Efficient Strategies for the Conjugation of Oligonucleotides to Antibodies Enabling Highly Sensitive Protein Detection, Wiley InterScience (www.interscience.wiley.com) Mar. 8, 2004, pp. 621-630. [cited by applicant]
Liangcai G. et al., “Multiplex single-molecule interaction profiling of DN ••barcoded proteins”, Nature, vol. 515, No. 7528, Nov. 1, 2014, pp. 554-557. [cited by applicant]
Lipovsek, et al., “In-vitro protein evolution by ribosome display and mRNA display,” J. Immunol. Methods (2004), , doi:10.1016/j.jim.2004.04.008. [cited by applicant]
Mchugh, Colleen A. et al.; “The Xist IncRNA interacts directly with SHARP to silence transcription through HDAC3”; Nature; vol. 521; May 14, 2015; 24pp. [cited by applicant]
Proschel, M., Probing the Potential of CnaB-type Domains for the Design of Tag/Catcher Systems, PLoS One 12(6):e0179740 (2017). [cited by applicant]
Quinodoz, S. et al., Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus. Cell. vol. 174, Jul. 26, 2018, pp. 744-757. [cited by applicant]
Singh, et al., “Genetically encoded multispectral labeling of proteins with polyfluorophores on a DNA backbone,” J. Am. Chem. Soc. (2013), doi: 10.1021/ja4004393. [cited by applicant]
Solulink, “Antibody-Oligonucleotide Conjugate Preparation”, Solulink.com, 4 pages, year 2012. [cited by applicant]
Takahashi, et al., “mRNA display: Ligand discovery, interaction analysis and beyond,” Trends Biochem. Sci. (2003), doi:10.1016/S0968-0004(03)00036-7. [cited by applicant]
Tan et al., Kinetic Controlled Tag-Catcher Interactions for Directed Covalent Protein Assembly, PLOS one, Oct. 26, 2016, 15 pages. [cited by applicant]
Veggiani et al., Programmable Polyproteams built using twin peptide superglues, PNAS, Feb. 2, 2016, 6 pages, vol. 113 No. 5. [cited by applicant]
Williams, B. et al., Synthesis of Peptide-Oligonucleotide Conjugates Using a Heterobifunctional Crosslinker. Current Protocols in Nucleic Acid Chemistry. Chapter: Unit 4.41. Sep. 2010. [cited by applicant]
Williams, et al., “Synthesis of peptide-oligonucleotide conjugates using a heterobifunctional crosslinker,” Curr. Protoc. Nucleic Acid Chem. (2010), ,doi: 10.1002/0471142700.nc0441s42. [cited by applicant]
Wilson, et al., “The use of mRNA display to select high-affinity protein-binding peptides,” Proc. Natl. Acad. Sci. (2001), doi:10.1073/pnas.061028198. [cited by applicant]
Wolin, E. et al., “SPIDR: a highly multiplexed method for mapping RNA-protein interactions uncovers a potential mechanism for selective translational suppression upon cellular stress”, bioRxiv, Jun. 7, 2023, pp. 1-30. [cited by applicant]
Ya Z. et al., “SpyCLIP: an easy-to-use and high-throughput compatible CLIP platform for the characterization of protein-RNA interactions with high accuracy”, Nucleic Acids Research, vol. 47, No. 6, Jan. 31, 2019, pp. e3… [cited by applicant]
Ya Z. et al., “SpyCLIP: an easy-to-use and high-throughput compatible CLIP platform for the characterization of protein-RNA interactions with high accuracy; Supplementary figures and protocols.”, Nucleic Acids Research,… [cited by applicant]
Zakeri et al., Spontaneous Intermolecular Amide Bond Formation between Side Chains for Irreversible Peptide Targeting, Journal of the American Chemical Society, Mar. 17, 2010 (via web), 2 paaes, vol. 132 No. 13. [cited by applicant]