WO2021181221A1

WO2021181221A1 - Small molecules for regulation of long non-coding rnas

Info

Publication number: WO2021181221A1
Application number: PCT/IB2021/051814
Authority: WO
Inventors: Micha Drukker; Markus Oliver GROSCH
Original assignee: Cellido Therapeutics B.V.
Priority date: 2020-03-11
Filing date: 2021-03-04
Publication date: 2021-09-16

Abstract

The present disclosure describes compounds that can promote the disintegration of complexes containing long non-coding RNA (lncRNA) in vivo. The present disclosure provides a method of using small molecules to treat human diseases, wherein the small molecules are used to disintegrate nuclear condensates comprising lncRNAs. Further, the present disclosure provides an in vitro method of identifying small molecules for the treatment of human diseases associated with lncRNA.

Description

SMALL MOLECULES FOR REGULATION OF LONG NON-CODING RNAs SEQUENCE LISTING STATEMENT [1] The instant application contains a Sequence Listing, which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on March 2, 2021, is named P-594030-PC-SEQ-LIST-02MAR21 and is 40.1 Kilobytes in size. BACKGROUND [2] The human genome encodes for tens of thousands of long non-coding RNAs (lncRNAs), and researches have just begun revealing their regulatory functions in development, disease and homeostasis. Nuclear lncRNAs have been implicated in the regulation of gene expression in several ways, including the recruitment of chromatin remodeling complexes of the SWI/SNF family, and interaction with Polycomb repressive complexes, which modify histones. Importantly, many nuclear lncRNAs have been reported to form condensates, named collectively “membraneless organelles”. According to Mullard (Mullard (2019) Nature Reviews “Biomelecular condensates pique drug discovery curiosity”, 18:324-326) biomolecular condensates are “transient liquid-like droplets made up of proteins and RNA”. Further, it is suggested that these “membraneless organelles, which form through a process called liquid-liquid phse separation, are important in health and disease” (Mullard (2019) ibid). [3] A notable example of these membraneless organelles lncRNA condensates including paraspeckles, which comprise the lncRNA NEAT1 and RNA binding proteins (RBPs) that influence gene expression by post-transcriptional regulation of splicing and polyadenylation, as well as by interaction with the SWI/SNF complex that remodels nucleosomes. Similarly, the lncRNA MALAT1, which also forms condensates, has been shown to regulate gene expression by interactions with splicing factors, hence named splicing speckles. Despite advancements in understanding the composition and formation of lncRNA-protein condensates and separately the functions of cognate RBPs, for example TDP-43 in the regulation of alternative polyadenylation, the regulation mediated by the aggregation of lncRNAs, RBPs and other factors is poorly understood. [4] Nuclear lncRNAs and presumably lncRNA condensates such as paraspeckles, can be tethered to double-stranded DNA by forming RNA-dsDNA triple helix complexes, and such interactions have been proposed to rely on sequence-specific, base-pairing interactions. Whether such interactions are the basis for the location of hundreds of associations with open chromatin that were reported for lncRNAs such as NEAT1 and MALAT1 is an open question. [5] Mullard notes that the hunt for small molecules that could potentially control condensate biology has eluded researches and “remains frustrating”. Herein, a novel strategy is presented and exemplified that could assist in elucidating the underlying mechanisms of interactions between lncRNA and chromatin, which is the identification of compounds that alter the structure of dsDNA. Plausible types of small molecules include DNA-binding compounds from the Hoechst family and a host of other minor groove-associating molecules that are used for chemotherapy, such as Actinomycin D (ActD). [6] The use of human pluripotent stem cells (PSCs) for studying the functions of lncRNA condensates is advantageous in several respects: first, the differentiation of human PSCs (hPSCs) is accompanied by changes of the genome architecture that creates opportunities to study the formation of lncRNA condensates in cell fate transitions, as has been shown recently for paraspeckles (M. Modic et al., “Cross-Regulation between TDP-43 and Paraspeckles Promotes Pluripotency-Differentiation Transition,” Mol. Cell, vol. 74, no. 5, pp. 951-965.e13, Jun. 2019, doi: 10.1016/j.molcel.2019.03.041.). Second, differentiation protocols allow the generation of cell types from the three embryonic germ layers in order to analyze and compare general and cell type- specific regulation, for example using differentiated neurons, hepatocytes and cardiomyocytes. In this respect, it has been recently observed that the number of paraspeckles exhibited by cells during early differentiation of mouse and human PSCs is variable despite the robustness of differentiation protocols in creating homogenous differentiated cell preparations, and similar observations have been made previously in tumor cell lines. This indicates that an unknown form of structural regulation causes the seemingly random appearance of paraspeckles in cells, which could be linked to general mechanisms that regulate the vastly different number of paraspeckles observed in different cell types and upon exit from pluripotency. [7] Multiple lines of evidence increasingly link lncRNA condensates to diverse human diseases. In certain cases, mutations and dysregulations of lncRNAs is thought to mediate disease pathogenesis. The link between lncRNAs and diverse human disease challenges the concept that protein-coding genes are the sole contributors to the development of human disease. Diseases that have been associated with lncRNA include neurological diseases such as schizophrenia, bipolar disorder, cerebral ischemia, Alzheimer’s disease, and Huntington’s disease; cancers such as hepatocellular carcinoma, cardiac disease, and diabetes. [8] Long non-coding RNAs (lncRNAs) condensates, including paraspeckle condensates, comprising lncRNA condensates that are associated with human diseases may provide an unexpected and unique therapeutic target for these human diseases. Molecules that disintegrate or disrupt these lncRNA condensates could have therapeutic potential. To date, compounds that can disintegrate or disrupt lncRNA condensates in vivo have not been identified. [9] Thus, there remains an unmet need for methods of treatment of human diseases and conditions associated with lncRNA condensates including neurological diseases such as schizophrenia, bipolar disorder, cerebral ischemia, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease; cancers such as hepatocellular carcinoma, cardiac disease, and autoimmune diseases such as diabetes. The surprising discovery that dsDNA binding small molecules may disintegrate lncRNA condensates, including paraspeckle condensates, provide a pool of FDA approved drugs for chemotherapy, that could be repurposed for treating diseases involving aberrant formation of lncRNA condensates. SUMMARY [10] In some aspects, presented herein are methods of treating a human disease or condition associated with long non-coding RNA (lncRNA) condensates, said method comprising administering to a subject in need thereof a therapeutically effective amount of a small molecule that binds to double stranded DNA (dsDNA) and disintegrates or disrupts lncRNA condensates of a lncRNA-dsDNA complex, thereby treating the human disease or condition. [11] In some aspects, presented herein are compositions comprising a small molecule that binds to double stranded DNA (dsDNA) and disintegrates or disrupts lncRNA condensates of a lncRNA-dsDNA complex, for use treating a human disease or condition associated with long non- coding RNA (lncRNA) condensates. [12] In a related aspect, the small molecule binding comprises minor groove binding of the dsDNA, both major and minor groove binding of the dsDNA, or intercalating within the dsDNA. In further related aspect, the binding comprises (a) non-sequence specific binding; (b) structural specific binding; (c) binding that does not inhibit RNA transcription; or (d) binding that introduces a double strand break in the DNA; or (e) any combination thereof. In yet a further related aspect, the binding disintegrates or disrupts or a combination thereof, a lncRNA condensate. [13] In another related aspect, the lncRNA condensate comprises a paraspeckle. [14] In another related aspect, the lncRNA is selected from the group consisting of PVT1, KCNQ1OT1, AIRN, PINT, Linc-Pint, MALAT1, TERC, MEG3, LINC00472, TUG1, KLRA1P, PINCR, MANTIS, LncPRESS1, HAND2-AS, HOTAIR, HOTTIP, Braveheart, Fendrr, ANRIL, Chaer, pRNA, Dum, PAPAS, Xist, Air, Dali, LincRNA-p21, CCND-Nat, MIAT, ecCEBPA, RMRP, PANDA, H19, TARID, SLERT, FIRRE, ANRASSF1, PARTICLE, APTR, NEAT1_2, or any combination thereof. [15] In another related aspect, the small molecule comprises a chemotherapeutic agent. In another related aspect, the small molecule comprises an anthracycline drug. In a further related aspect, the small molecule comprises Actinomycin D (ActD), Doxorubicin, Mithramycin A, Mitomycin, Mitoxantrone, Etoposide, or Flavopriridol. [16] In another related aspect, the human disease or condition comprises a cancer, a neurological disease, an autoimmune disease, or a cardiac disease or condition. In a further related aspect, the cancer comprises Wilms' tumor, a childhood rhabdomyosarcoma, a Ewing's sarcoma or metastatic growth thereof, comprises a lymphoma, a non-lymphocytic leukemia, small cell lung cancer, or a glioblastoma multiforme, refractory testicular tumors, non-seminomatous testicular cancer, testicular cancer, hypercalcemia and hypercalciuria associated with an advanced form of a cancer a lymphoblastic leukemia, an acute myeloblastic leukemia, a Wilms’ tumor, neuroblastoma, a soft tissue and bone sarcoma, a breast carcinoma, an ovarian carcinoma, a transitional cell bladder carcinoma, a thyroid carcinoma, a gastric carcinoma, a Hodgkin’s disease, a malignant lymphoma or a bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types, an esophageal cancer, a leukemia (lymphoid), a lung cancer, a liver cancer, axillary lymph node involvement following resection of primary breast cancer, or a malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, or urinary bladder. In another further related aspect, the neurological disease or condition comprises schizophrenia, bipolar disorder, cerebral ischemia, frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple system atrophy, spinal muscular atrophy, multiple sclerosis, Cerebral Palsy, Autism Spectrum Disorder, Epilepsy, secondary (chronic) progressive multiple sclerosis, a progressive relapsing multiple sclerosis, or a worsening relapsing-remitting multiple sclerosis or Huntington’s disease. In yet another related aspect, the autoimmune disease comprises diabetes. [17] In a related aspect, the small molecule is ActD and said cancer comprises a Wilms' tumor, a childhood rhabdomyosarcoma, a Ewing's sarcoma or metastatic growth thereof, or a non- seminomatous testicular cancer. In a further related aspect, treating comprises a part of a combination chemotherapy and/or multi-modality treatment regimen. [18] In a related aspect, the small molecule is Doxorubicin and said cancer comprises a lymphoblastic leukemia, an acute myeloblastic leukemia, a Wilms’ tumor, neuroblastoma, a soft tissue and bone sarcoma, a breast carcinoma, a primary breast cancer, an ovarian carcinoma, a transitional cell bladder carcinoma, a thyroid carcinoma, a gastric carcinoma, a Hodgkin’s disease, a malignant lymphoma, or a bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. In a further related aspect, when said subject is female and said cancer comprises axillary lymph node involvement following resection of primary breast cancer, said treating comprises an adjuvant therapy. [19] In a related aspect, the small molecule is Mithramycin A and said cancer comprises testicular cancer, or hypercalcemia and hypercalciuria associated with an advanced form of a cancer. [20] In a related aspect, the small molecule is Mitomycin and said cancer comprises a malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, or urinary bladder. [21] In a related aspect, the small molecule is Etoposide and said cancer comprises a lymphoma, a non-lymphocytic leukemia, a small cell lung cancer, or a glioblastoma multiform, or said use is in combination with other chemotherapeutic agents and said cancer comprises refractory testicular tumors. [22] In a related aspect, the small molecule is Flavorpiridol and said cancer comprises an esophageal cancer, a leukemia (lymphoid), a lung cancer, a liver cancer, or a lymphoma. [23] In a related aspect, the small molecule is Mitoxantrone and said neurological disease comprises secondary (chronic) progressive multiple sclerosis, a progressive relapsing multiple sclerosis, or a worsening relapsing-remitting multiple sclerosis. [24] In some aspects, presented herein are in vitro method of identifying a treatment agent for a human subject suffering from a disease or condition associated with a long non-coding RNA (lncRNA) condensate, said method comprising (a) collecting a biological sample comprising cells from the subject suffering from said disease or conditions associated with a lncRNA condensate; (b) culturing a portion of said cells of said biological sample with a small molecule that binds to double stranded DNA (dsDNA) and culturing a control portion of said cells without said small molecule; (c) incubating said cultures under physiological conditions for a period of time; (d) measuring the number and size of lncRNA condensates present in the portion of cells incubated with said small molecule and in the control portion of cells; and (e) comparing the number and size of the lncRNA condensates present in both portions, and determining if the number or size or both of said lncRNA condensates is reduced in the portion incubated with the small molecule; wherein if the number or size or both of said lncRNA condensates is reduced in the portion incubated with the small molecule compared with the control portion, then the small molecule is identified as a treatment agent for said subject. In a further related aspect, the binding comprises minor groove binding of said dsDNA, both major and minor groove binding of said dsDNA, or intercalating within said dsDNA. In yet a further related aspect, the binding comprises (a) non- sequence specific binding; (b) structural specific binding; (c) binding that does not inhibit RNA transcription; or (d) binding that introduces a double strand break in the DNA; or (e) any combination thereof. [25] In a related aspect, the lncRNA condensate comprises a paraspeckle. [26] In a related aspect, the biological sample comprises urine, blood, a tissue biopsy, or a tumor tissue biopsy. [27] In a related aspect, the cells comprise an intact nucleus. In a further related aspect, the cells comprise peripheral blood mononuclear cells (PBMC),adult fibroblasts, neonatal fibroblasts, neural crest cells, mesenchymal stem cells, adipocytes, myotubes, nephron progenitor cells, nephrons, osteocytes, cardiomyocytes, lung progenitor cells, hepatocytes, neural stem cells, motor neurons, astrocytes, cortical neuron progenitor cells, cortical neurons, neural stem cells, keratinocytes, trophoblast progenitor cells, endoderm cells, mesoderm cells, or any combination thereof. [28] In a related aspect, the incubation comprises incubating for about 1 to 30 days. [29] In a related aspect, the binding disintegrates or disrupts or a combination thereof, a lncRNA condensate. In a further related aspect, the lncRNA is selected from the group consisting of PVT1, KCNQ1OT1, AIRN, PINT, Linc-Pint, MALAT1, TERC, MEG3, LINC00472, TUG1, KLRA1P, PINCR, MANTIS, LncPRESS1, HAND2-AS, HOTAIR, HOTTIP, Braveheart, Fendrr, ANRIL, Chaer, pRNA, Dum, PAPAS, Xist, Air, Dali, LincRNA-p21, CCND-Nat, MIAT, ecCEBPA, RMRP, PANDA, H19, TARID, SLERT, FIRRE, ANRASSF1, PARTICLE, APTR, NEAT1_2, or any combination thereof. [30] In a related aspect, the small molecule comprises a chemotherapeutic agent. In a related aspect, the small molecule comprises an anthracycline agent. In a further related aspect, the small molecule comprises Actinomycin D (ActD), Doxorubicin, Mithramycin A, Mitomycin, Mitoxantrone, Etoposide, or Flavopriridol. [31] In a related aspect, the human disease or condition comprises cancer, a neurological disease, an autoimmune disease, or a cardiac disease or condition. [32] In a related aspect, when the method of identification identifies the small molecule as a treatment agent for said subject, the method comprises a further treating step (f), comprising administering to the subject a therapeutically effective amount of a composition comprising the identified small molecule. [33] In a further related aspect, the human disease or condition comprises a cancer and ActD is identified as a treatment agent for said subject, said method comprises a further treating step (f), comprising administering to the subject a therapeutically effective amount of a composition comprising ActD, thereby treating the human disease or condition. In a yet further related aspect, the cancer comprises of a Wilms' tumor, a childhood rhabdomyosarcoma, a Ewing's sarcoma or metastatic growth thereof, a non-seminomatous testicular cancer. In still a further related aspect, the treating comprises a part of a combination chemotherapy and/or multi-modality treatment regimen. [34] In a further related aspect, the human disease or condition comprises a cancer and Doxorubicin is identified as a treatment agent for said subject, said method comprises a further treating step (f), comprising administering to the subject a therapeutically effective amount of a composition comprising Doxorubicin, thereby treating the human disease or condition. In yet a further related aspect, the cancer comprises a lymphoblastic leukemia, an acute myeloblastic leukemia, a Wilms’ tumor, neuroblastoma, a soft tissue and bone sarcoma, a breast carcinoma, an ovarian carcinoma, a transitional cell bladder carcinoma, a thyroid carcinoma, a gastric carcinoma, a Hodgkin’s disease, a malignant lymphoma or a bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. In still a further related aspect, the subject is female and said cancer comprises axillary lymph node involvement following resection of primary breast cancer and said treating comprises an adjuvant therapy. [35] In a further related aspect, the human disease or condition comprises a cancer and Mithramycin A is identified as a treatment agent for said subject, said method comprises a further treating step (f), comprising administering to the subject a therapeutically effective amount of a composition comprising Mithramycin, thereby treating the human disease or condition. In yet a further related aspect, the cancer comprises testicular cancer, or hypercalcemia and hypercalciuria associated with an advanced form of a cancer. [36] In a further related aspect, the human disease or condition comprises a cancer and Mitomycin is identified as a treatment agent for said subject, said method comprises a further treating step (f), comprising administering to the subject a therapeutically effective amount of a composition comprising Mitomycin, thereby treating the human disease or condition. In yet a further related aspect, the cancer comprises a malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, or urinary bladder. [37] In a further related aspect, the human disease or condition comprises a cancer and Etoposide is identified as a treatment agent for said subject, said method comprises a further treating step (f), comprising administering to the subject a therapeutically effective amount of a composition comprising Etoposide, thereby treating the human disease or condition. In yet a further related aspect, the cancer comprises a lymphoma, a non-lymphocytic leukemia, small cell lung cancer, or a glioblastoma multiform, or said treating is used in combination with other chemotherapeutic agents and said cancer comprises refractory testicular tumors. [38] In a further related aspect, the human disease or condition comprises a neurological disease or condition and Mitoxantrone is identified as a treatment agent for said subject, said method comprises a further treating step (f), comprising administering to the subject a therapeutically effective amount of a composition comprising Mitoxantrone, thereby treating the human disease or condition. In yet a further related aspect, the neurological disease comprises secondary (chronic) progressive multiple sclerosis, a progressive relapsing multiple sclerosis, or a worsening relapsing-remitting multiple sclerosis. [39] In a further related aspect, the human disease or condition comprises a cancer and Flavorpiridol is identified as a treatment agent for said subject, said method comprises a further treating step (f), comprising administering to the subject a therapeutically effective amount of a composition comprising Flavorpiridol, thereby treating the human disease or condition. In yet a further related aspect, the cancer comprises an esophageal cancer, a leukemia (lymphoid), a lung cancer, a liver cancer, or a lymphoma [40] In a further related aspect, the neurological disease or condition comprises schizophrenia, bipolar disorder, cerebral ischemia, frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple system atrophy, spinal muscular atrophy, multiple sclerosis, Cerebral Palsy, Autism Spectrum Disorder, Epilepsy, or Huntington’s disease. [41] In a further related aspect, the autoimmune disease comprises diabetes. BRIEF DESCRIPTION OF THE DRAWINGS [42] The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. [43] The subject matter regarded as the disclosure of methods of use described herein are particularly pointed out and distinctly claimed in the concluding portion of the specification. The methods of use, however, both as to organization and method of operation, together with objects, features, and advantages thereof, may best be understood by reference to the following detailed description when read with the accompanying drawings in which: [44] Figures 1A-1F presents characterization of developmentally regulated lncRNAs. Figure 1A shows a scheme illustrating the cell types that were produced in this study by differentiation of human pluripotent stem cells (hPSCs). Starting with undifferentiated cells at the top, hPSCs were differentiated to precursors of the germ layers, embryonic and extraembryonic progenitors, and terminally differentiated cells. The lineage and approximate developmental distances were estimated based on the expression of developmental markers as outlined herein and in Figure 6A- 6O. In addition, primary preparations of keratinocytes, fibroblasts (adult and newborn origin) and myotubes were analyzed. Figures 1B-1D show the RT-qPCR analysis of lineage-selected markers corresponding to lateral mesoderm, and mesenchymal stem cells (Figure 1B); definitive endoderm and lung progenitors (Figure 1C); and neural progenitors and cortical neuron progenitors (Figure 1D). Pluripotency genes OCT4, SOX2 and NANOG were analyzed in all samples. n=2 independent experiments. Figures 1E and 1F show the absolute (Figure 1E) and relative (Figure 1F) expression of nuclear long non-coding RNAs (lncRNAs) in undifferentiated human embryonic stem cells (ESCs) and germ layer and tissue progenitors as in Figures 1B-1D based on RT-qPCR analysis. n=3 independent experiments, error bars represent standard deviation, p-values were calculated by unpaired t-test; * p < 0.05, ** p < 0.01, *** p < 0.001, **** p< 0.0001. Cells at different passages were used for replicates. Abbreviations: LM: lateral mesoderm, MSC: mesenchymal stem cells, DE: definitive endoderm, LP: lung progenitors, CNP: cortical neuron progenitors, NSC: neural stem cells. [45] Figures 2A-2D presents the characterization of paraspeckles in a panel of cell types and differentiated states. Figure 2A shows a representative immunocytochemistry images of terminally differentiated cell preparations stained with antibodies, specific for markers of the respective cell types (scale bar upper panels: 50 μm) and analyzed by smFISH with NEAT1_2 probe (bottom panel, probe in red, DAPI staining in blue; scale bar: 10 μm). Figure 2B shows a summary of paraspeckle amounts in diverse developmental and terminally differentiated cell types, and during reprogramming of human newborn fibroblasts (Figures 7H-7J). Size of circles corresponds to the average number of paraspeckles in the different cell types which was quantified by automated spot (foci) detection in a total of 200 - 2000 cells per type representing 3 independent experiments (Single data points and statistics in Figure 7C). Figure 2C shows Violin plots depicting the number of paraspeckles in 100 single cells from all tested human cell types based on (Figure 2B), black line represents mean value and dashed lines the quartiles. Figure 2D shows quantification of paraspeckle in primary murine cell types (n=3 independent replicates using ESCs, or 3 different mice for the other cell types). Representative images in Figure 7E shown next to the corresponding human cell populations from (Figure 2B). Error bars represent standard deviation, **** p<0.0001 unpaired t-test. [46] Figures 3A-3J presents paraspeckle formation correlates with size of nucleus. Figure 3A shows images and quantification of nuclear area (μm2) by DAPI staining (blue) and number of NEAT1_2 foci analyzed by smFISH (red) of representative human adult newborn fibroblasts that exhibited different sizes (scale bar: 10 μm). Figure 3B shows analysis of the correlation between the number of paraspeckles and nucleus size of 100 human newborn (black) and adult (grey) fibroblasts. Figure 3C shows analysis of the correlation between the averaged number of paraspeckles and averaged nucleus size per cell in 24 cell types analyzed in the atlas database represented in Figure 2B. Figure 3D shows averaged nucleus size (black) and number of paraspeckles (red; based on Figure 2B) analyzed during reprogramming of human newborn fibroblasts. Figures 3E-3H) shows averaged number of paraspeckles per cell (Figures 3E, 3G) based on Figures 2B and 2D and averaged nuclear size (Figures 3F, 3H) in mouse (grey) and human (black) MSCs and astrocytes (AC), as well as in adult (grey) and newborn (black) fibroblasts. Numbers on top are the fold changes between the respective cell types from the human and the mouse. The numbers in red represent predicted fold changes based on slope of regression line in Figure 3C. Figures 3I and 3J show averaged number of paraspeckles per cell (Figure 3I) and averaged nuclear size (Figure 3J) of NEAT1^-/-, NEAT1ΔpA and WT hESCs in pluripotent condition or differentiated by addition of retinoic acid for 3 days to induce paraspeckle formation. Nucleus size represent the averaged value of 7-14 images per cell type from 2 independent experiments with 10-100 cells per image (details in methods). Error bars represent standard error of the mean. r in Figures 3B and 3C represents the Pearson`s correlation coefficient and dashed line is the linear regression line. [47] Figures 4A-4F present data showing that treatment with DNA-binding small molecules promotes paraspeckle disassembly. Figures 4A and 4B show representative images of NEAT1_2 smFISH after treatment of cells by 2 μM ActD (Figure 4A), 100 μg/ml Hoechst 33342, 5 μM Mithramycin A and 50 μM α-Amanitin (Figure 4B) in trophoblast progenitors produced by 3 day BMP4 treatments of hESCs. Dashed lines show the locations of the borders of the nuclei. Scale bar: 10 μm. Figure 4C shows analysis of the averaged amount of NEAT1_2 foci following ActD treatment in 5 different cell types. Images in Figure 8A. Figure 4D shows analysis of the averaged amount of NEAT1_2 foci in trophoblast progenitors following treatment by the four chemicals shown in Figures 4A and 4B. Figure 4E shows quantification of γ-H2AX foci indicating DNA double strand breaks in trophoblast progenitors and after addition of small DNA binding molecules. Representative images in Figure 8D. Figures 4F shows analysis of the averaged amount of NEAT1_2 foci in trophoblast progenitors following 2 h of treatment by the chemicals in Figure 4E and different concentrations of the chemotherapeutic reagents Vincristine, Etoposide and Flavopiridol. DNA binding and transcriptional inhibition properties of used chemicals are listed in Figure 8D. Error bars in Figures 4C and 4D represent standard error of the mean and standard deviation in Figures 4E and 4F.7 images were analyzed in Figures 4E and 4F and 14 in Figures 4C and 4D, representing 2 independent replicates using cells of different passages. **** p< 0.0001 unpaired t-test. [48] Figures 5A-5I present NEAT1_2 depletion increases differentiation potential. Figure 5A show the strategy of generating NEAT1-/-, NEAT1STOP and NEAT1ΔTH hESC clones by CRISPR/Cas9. Figures 5B-5D show representative images (Figure 5B) and quantification of paraspeckles by smFISH with NEAT1_2 (red) probe (Figure 5C) or RT-qPCR (Figure 5D) in parental (WT), NEAT1ΔTH, NEAT1-/- and NEAT1STOP hESCs after 3 days of differentiation induced by retinoic acid (Figures 5B and 5C) or spontaneous differentiation (Figure 5D). Primers for NEAT1_t(otal) target both NEAT1 isoforms. DAPI staining in blue; scale bar: 10 μm. Figures 5E-5I show RT-qPCR of pluripotency and differentiation markers (Figure 5E), and flow cytometry of pluripotency markers after WT, NEAT1ΔTH and NEAT1-/- hESCs were spontaneously differentiated for 3 days (Figures 5F and 5G) or after 4 days of neuroectoderm differentiation (Figures 5H and 5I). NEAT1STOP hESCs were included in Figure 5E. n=2 independent experiments using cells of different passages and with 3 knock-out clones per cell line. Forward and side scatter gating was employed to gate out debris and cell clumps. Error bars represent standard deviation in Figures 5C-5E or standard error of the mean in Figures 5G and 5H. * p < 0.05, ** p < 0.01, *** p < 0.001, **** p< 0.0001, unpaired t-test. [49] Figures 6A-6O present characterization of germ layer progenitors and differentiated cells. Figure 6A shows analysis of mesoderm differentiation towards mesenchymal stem cells (MSCs) showing the expression of characteristic markers CD73 and CD90 in accordance to (T. L Ramos et al., “MSC surface markers (CD44, CD73, and CD90) can identify human MSC-derived extracellular vesicles by conventional flow cytometry,” Cell Commun. Signal, vol. 14, p. 2, Jan. 2016, doi: 10.1186/s12964-015-0124-8). Figures 6B-6D show analysis of the differentiation towards definitive endoderm showing the up-regulation of CXCR4, EPCAM and CD117 cell surface markers (Figure 6B) and a cohort of characteristic markers as well as the downregulation of pluripotency genes by RT-qPCR (Figure 6C), and the expression of eGFP integrated in NKX2.1, which marks the formation of human lung progenitors (Figure 6D). Scale bar: 10 μm. Figures 6E and 6F show representative immunocytochemistry images of NSCs showing the expression of characteristic markers PAX6, SOX1 and NESTIN on day 21 of NSC differentiation (Figure 6E), and the cortical neuron progenitor markers FOXG1 and PAX6 (Figure 6F). Scale bar: 50 μm. Figures 6G and 6H show Oil Red O (Figure 6G) and Alizarin Red (Figure 6H) staining of human MSCs differentiated to adipocytes and osteocytes, respectively. Scale bar: 500 μm. Figures 6I and 6J show a time course RT-qPCR analysis of representative pluripotency, mesoderm and cardiac markers during lateral mesoderm differentiation to cardiomyocytes (Figure 6I), and of representative intermediate mesoderm and nephron progenitor markers during nephron differentiation (Figure 6J). Figure 6K shows representative images showing the expression of characteristic nephron progenitor markers CDH5 and WT1 at day 14 of differentiation. Figure 6L shows RT-qPCR analysis of representative pluripotency, definitive endoderm and hepatocyte markers during differentiation to hepatocytes at day 16 (30). Figures 6M-6O show RT-qPCR analysis of representative pluripotency, motor neuron, glial and cortical markers following differentiation to motor neurons (Figure 6M), astrocytes (Figure 6N) and cortical neurons (Figure 6O). n=2 independent experiments, error bars represent standard deviation, cells in different passages were used for replicates. [50] Figures 7A-7K present quantification of paraspeckles. Figures 7A and 7B show representative images of NEAT1_2 (red) in cells representing tissue progenitors (Figure 7A), and terminally differentiated cells (Figure 7B). Figure 7C shows the number of paraspeckles per cell in progenitors and differentiated cell types used to calculate the average number of paraspeckles in Figure 2B. Each dot represents the average of one microscopic image displaying 10-150 cells. n=3 independent replicates using cells of different passages were analyzed with 5-7 images per replicate. Changes in number of paraspeckles are statistically significant for all cell types compared to human ESCs (p < 0.0001, unpaired t-test; *** p < 0.001). Figure 7D shows the correlation of differentiation time as specified in the method section and averaged number of paraspeckles per cell type. Figure 7E shows representative images of NEAT1_2 (red) in mouse ESCs and primary cardiomyocytes, hepatocytes, MSCs and astrocytes, next to same cell types from the human. Figure 7F shows the correlation of NEAT1_2 total intensity and the number of paraspeckles per cell in representative human and mouse cell types. Each point represents a microscopic image. Figure 7G shows RT-qPCR of NEAT1_2 in 19 cell types and correlation with averaged number of paraspeckles per cell indicated in Figure 2B. RNA was obtained from 2-3 independent differentiations of cells in different passages. Figure 7H shows a time-course RT- qPCR analysis of endogenous transcription of pluripotency factors OCT4, SOX2 and NANOG during reprogramming of human newborn fibroblasts. n=2 independent reprogramming experiments. Figures 7I and 7J show representative brightfield (Figure 7I) and NEAT1_2 (Figure 7J) images taken during fibroblast reprogramming. n=2 independent reprogramming experiments using cells of different passages were analyzed with 7 images per replicate; nascent iPSC colonies are marked with white circles. Error bars represent standard deviation. DAPI staining in blue; scale bar is 10 μm in smFISH images and 50 μm in brightfield images. r in Figures 7D, 7F, and 7G represents the Pearson`s correlation coefficient. [51] Figures 8A-8F present characterization of lncRNA foci after treatment by Actinomycin D. Figure 8A shows representative images of NEAT1_2 smFISH after treatment of human ESC derived astrocytes, definitive endoderm cells, NSCs and primary newborn fibroblasts by 2 μM ActD. Figure 8B shows immunocytochemistry of nucleolar protein fibrillarin (FBL) and paraspeckle proteins SFPQ and NONO in untreated trophoblast progenitors and after treatment by 2 μM ActD for 1 hour. Figure 8C shows representative immunocytochemistry images of γ- H2AX foci indicating DNA double strand breaks in trophoblast progenitors and after addition of small DNA binding molecules. Quantification in Figure 4E. Concentrations as in Figures 4A and 4B. Figure 8D provides a table indicating the potential of small molecules used in this study to bind DNA, to inhibit transcription and to disintegrate paraspeckles. Figures 8E and 8F show representative images (Figure 8E) and quantification (Figure 8F) of MALAT1 smFISH in human trophoblast progenitors treated with ActD as above. n=2 independent replicates with 7 images per replicate. Dashed lines in Figure 8A and Figure 8F show the locations of the borders of the nuclei. [52] Figures 9A-9K present characterization of NEAT1-manipulated cells. Figure 9A shows RT-qPCR of pluripotency and differentiation markers of undifferentiated NEAT1-/-, NEAT1STOP and NEAT1ΔTH hESC clones. Figures 9B and 9C show flow cytometry analysis of pluripotency surface markers TRA1-60 and SSEA5 after 2 days of spontaneous differentiation of WT, NEAT1ΔTH and NEAT1-/- hESCs. Figure 9D shows RT-qPCR time course analysis of pluripotency and neural marker genes during differentiation towards neural rosettes which appeared around day 12 of the differentiation towards NSCs. Same cell lines as in Figures 9B and 9C. Figures 9E -9G show RT-qPCR analysis of NEAT1ΔpA hESC clones differentiated to lateral mesoderm (Figure 9E), definitive endoderm (Figure 9F) and neuroectoderm by 4 days differentiation of NSCs (Figure 9G). Figures 9H-9K show representative histograms and quantification of flow cytometry analysis for pluripotency markers in pluripotent (Figures 9H and 9J) NEAT1STOP hESCs and after 3 days of spontaneous differentiation (Figures 9I and 9K). Forward and side scatter gating was employed to gate out debris and cell clumps. n=2 independent experiments using cells of different passages with 3 knock-out clones per cell line expect in Figures 9A, 9J, and 9K where 3 experiments with 2 knock-out clones were performed. Error bars represent standard deviation. [53] Figure 10 presents a workflow review of the human PSC Differentiation Atlas and the use of small DNA binding molecules for disintegration of long non-coding RNA condensates. DETAILED DESCRIPTION [54] In the following detailed description, numerous specific details are set forth in order to provide a thorough understanding of long non-coding RNAs (lncRNA) condensates, their relationship with cell differentiation and disease, and uses of small molecules to disrupt or disintegrate lncRNA condensates, including paraspeckles. In certain instances, well-known methods, procedures, and components have not been described in detail so as not to obscure the present methods of use for treating a subject in need or for identifying a treatment agent. [55] In the human genome, the ratio of non-coding DNA to total genomic DNA is approximately 98.5%. Recent studies have revealed that transcription is not restricted to protein- coding regions, but occurs throughout the genome (>90%), including non-coding regions. This yields large numbers of non-coding RNAs (ncRNAs) (Tano and Akimitsu, Long Non-coding RNAs in Cancer Progression. Front Genet. 3:219 (2012)). Among these ncRNAs, long ncRNAs (lncRNAs) represent the most prevalent and functionally diverse class. The most commonly used definition for lncRNAs is based on the threshold of a length of 200 nucleotides (nt). It conventionally divides ncRNAs into lncRNAs that have more than 200 nt in length and the remaining ones that are considered “small” RNAs (Ma et al., On the Classification of Long Non- coding RNAs. RNA Biol.10:924–933 (2013)). [56] Recent advances in experimental and computational technologies make it feasible to conduct deep mining on more and more transcribed sequences. At present, there are 73,370 lncRNA entries from 1,239 organisms according to NONCODE v3.0, a database of literature documented lncRNAs (Ma et al., 2013, ibid). [57] One way to characterize the lncRNAs is to classify them according to genomic location— i.e., from where in the genome these RNAs are transcribed, relative to well-established markers such as protein-coding genes. In this manner, lncRNAs can be grouped into several broad but mutually nonexclusive categories. lncRNAs may be stand-alone transcription units; or they may be transcribed from enhancers, promoters, or introns of other genes; or transcribed from pseudogenes; or antisense to other genes with varying degrees of overlap (Kung et al., Long Noncoding RNAs: Past, Present, and Future. Genetics 193:651-669 (2013)). [58] A lot of evidence has accumulated showing that lncRNAs play a significant role in a wide variety of important biological processes, including transcription, splicing, translation, protein localization, cellular structure integrity, imprinting, cell cycle and apoptosis, stem cell pluripotency and reprogramming and heat shock response. It has also been suggested that lncRNAs may regulate cancer progression and development of many other human diseases (Ma et al., 2013, ibid). For example, MALAT1, also known as NEAT2 (nuclear-enriched abundant transcript 2), a lncRNA of more than 8000 nt, was the lncRNA that was originally found to be associated with lung cancer (Tano and Akimitsu, 2012, ibid). Hox antisense intergenic RNA (HOTAIR), also known as metastasis-associated lncRNA, is a 2.2-kb transcript. Expression of HOTAIR was increased in primary breast tumors and metastases. There is a positive correlation among high expression levels of HOTAIR, subsequent metastasis and death. Antisense non- coding RNA in the Ink4 locus (ANRIL) was first identified following genetic analysis of familial melanoma patients with neural system tumors who had a large germline deletion of the entire INK4B-ARF-INK4A gene cluster. ANRIL is transcribed as a 3.8-kb lncRNA in the opposite direction from the INK4B-ARF-INK4A gene cluster. Recent genome-wide association studies have identified ANRIL as a risk locus for several cancers, including breast cancer, nasopharyngeal carcinoma, basal cell carcinoma, and gliomas (Tano and Akimitsu, 2012, ibid). Methods of Use [59] Disclosed herein are methods of treating a human disease or condition associated with long non-coding RNA (lncRNA) condensates, wherein the method comprises administering to a subject in need thereof a therapeutically effective amount of a small molecule that binds to double stranded DNA (dsDNA) and disintegrates or disrupts lncRNA condensates of a lncRNA-dsDNA complex, thereby treating the human disease or condition. [60] Also, disclosed herein are in vitro methods of identifying a treatment agent for a human subject suffering from a disease or condition associated with a long non-coding RNA (lncRNA) condensates. In certain embodiments, following identification of a treatment agent, the method further includes treating a subject suffering from a human disease or condition associated with a lncRNA condensates. [61] In some embodiments, disclosed herein are in vitro methods of identifying a treatment agent for a human subject suffering from a disease or condition associated with a long non-coding RNA (lncRNA) condensate, said method comprising - collecting a biological sample comprising cells from the subject suffering from said disease or conditions associated with a lncRNA; - culturing a portion of said cells of said biological sample with a small molecule that binds to double stranded DNA (dsDNA) and culturing a control portion of said cells without said small molecule; - incubating said cultures under physiological conditions for a period of time; - measuring the number and size of lncRNA condensates present in the portion of cells incubated with said small molecule and in the control portion of cells; and - comparing the number and size of the lncRNA condensates present in both portions, and determining if the number or size or both of said lncRNA condensates is reduced in the portion incubated with the small molecule; wherein if the number or size or both of said lncRNA condensates is reduced in the portion incubated with the small molecule compared with the control, then the small molecule is identified as a treatment agent for said subject. [62] A skilled artisan would appreciate that “long non-coding RNA” or “lncRNA” encompass RNA molecules that are not translated into protein. In some embodiments, long non-coding RNAs encompass non-coding RNA transcripts longer than about 200 nucleotides. They have been shown to play an important role in gene transcription, post-transcriptional regulation and epigenetic regulation. [63] A data base curating human disease associated with lncRNA has been established (Bao, Zhenyu et al. “LncRNADisease 2.0: an updated database of long non-coding RNA-associated diseases.” Nucleic acids research vol.47,D1 (2019): D1034-D1037. doi:10.1093/nar/gky905). In some embodiments, a method of treating a human disease or condition associated with lncRNA condensates comprises a disease or condition described in the LncRNA Disease data base. [64] In some embodiments, a lncRNA condensate comprises nuclear membraneless organelles. A skilled artisan would appreciate that membranelss organelles may encompass ribonucleoprotein complexes. In some embodiments, a lncRNA condensate comprises a ribonucleoprotein complex. In some embodiments, a lncRNA condensate comprises a paraspeckle. In some embodiments, a paraspeckle comprises a ribonucleoprotein complex. In some embodiments, nuclear membraneless organelles comprise paraspeckels. [65] In some embodiments, a lncRNA is tethered to chromatin. In some embodiments, a lncRNA condensate is tether to chromatin. A skilled artisan would appreciate that in certain embodiments the term “tethering” may encompass an association with chromatin, a binding with chromatin, an integration with chromatin, or an anchoring with chromatin. Thus, in certain embodiments, a lncRNA is associated with chromatin. In some embodiments, a lncRNA condensate is associated with chromatin. In certain embodiments, a lncRNA is bound to chromatin. In some embodiments, a lncRNA condensate is bound to chromatin. In certain embodiments, a lncRNA is integrated within chromatin. In some embodiments, a lncRNA condensate is integrated within chromatin. In certain embodiments, a lncRNA is anchored within chromatin. In some embodiments, a lncRNA condensate is anchored within chromatin. [66] In some embodiments, a paraspeckle is tethered to chromatin. In some embodiments, a ribonucleoprotein comprising a lncRNA is tether to chromatin. In certain embodiments, a paraspeckle is associated with chromatin. In some embodiments, a ribonucleoprotein comprising a lncRNA is associated with chromatin. In certain embodiments, a paraspeckle is bound to chromatin. In some embodiments, a ribonucleoprotein comprising a lncRNA is bound to chromatin. In certain embodiments, a paraspeckle is integrated within chromatin. In some embodiments, a ribonucleoprotein comprising a lncRNA is integrated within chromatin. In certain embodiments, a paraspeckle is anchored within chromatin. In some embodiments, a ribonucleoprotein comprising a lncRNA is anchored within chromatin. [67] In certain embodiments, lncRNA are tethered to triple helix DNA in the cell nucleus. In some embodiments, a lncRNA tethered to double stranded DNA (dsDNA) comprises a lncRNA condensate. In certain embodiments, a ribonucleoprotein comprising lncRNA are tethered to triple helix DNA in the cell nucleus. In some embodiments, a ribonucleoprotein comprising lncRNA tethered to double stranded DNA (dsDNA) comprises a lncRNA condensate. In some embodiments, a ribonucleoprotein comprising lncRNA tethered to double stranded DNA (dsDNA) comprising a lncRNA condensate, comprises a paraspeckle. [68] In some embodiments, non-limiting examples of nuclear tethered lncRNA molecules comprise PVT1, KCNQ1OT1, AIRN, PINT, Linc-Pint, MALAT1, TERC, MEG3, LINC00472, TUG1, KLRA1P, PINCR, MANTIS, LncPRESS1, HAND2-AS, HOTAIR, HOTTIP, Braveheart, Fendrr, ANRIL, Chaer, pRNA, Dum, PAPAS, Xist, Air, Dali, LincRNA-p21, CCND- Nat, MIAT, ecCEBPA, RMRP, PANDA, H19, TARID, SLERT, FIRRE, ANRASSF1, PARTICLE, APTR, or NEAT1_2, or any combination thereof. In some embodiments, a nuclear tethered lncRNA molecule comprises NEAT1_2. [69] In some embodiments of methods disclosed herein for treating a human disease or condition associated with lncRNA condensates, the lncRNA comprises PVT1, KCNQ1OT1, AIRN, PINT, Linc-Pint, MALAT1, TERC, MEG3, LINC00472, TUG1, KLRA1P, PINCR, MANTIS, LncPRESS1, HAND2-AS, HOTAIR, HOTTIP, Braveheart, Fendrr, ANRIL, Chaer, pRNA, Dum, PAPAS, Xist, Air, Dali, LincRNA-p21, CCND-Nat, MIAT, ecCEBPA, RMRP, PANDA, H19, TARID, SLERT, FIRRE, ANRASSF1, PARTICLE, APTR, or NEAT1_2, or any combination thereof. In some embodiments of methods disclosed herein identifying a treatment agent for treating a human disease or condition associated with lncRNA condensates, the lncRNA comprises PVT1, KCNQ1OT1, AIRN, PINT, Linc-Pint, MALAT1, TERC, MEG3, LINC00472, TUG1, KLRA1P, PINCR, MANTIS, LncPRESS1, HAND2-AS, HOTAIR, HOTTIP, Braveheart, Fendrr, ANRIL, Chaer, pRNA, Dum, PAPAS, Xist, Air, Dali, LincRNA-p21, CCND- Nat, MIAT, ecCEBPA, RMRP, PANDA, H19, TARID, SLERT, FIRRE, ANRASSF1, PARTICLE, APTR, or NEAT1_2, or any combination thereof. [70] In some embodiments, a nuclear tethered lncRNA comprises PVT1 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises KCNQ1OT1 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises AIRN lncRNA. In some embodiments, a nuclear tethered lncRNA comprises PINT lncRNA. In some embodiments, a nuclear tethered lncRNA comprises Linc-Pint lncRNA. In some embodiments, a nuclear tethered lncRNA comprises MALAT1 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises TERC lncRNA. In some embodiments, a nuclear tethered lncRNA comprises MEG3 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises LINC00472 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises TUG1 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises KLRA1P lncRNA. In some embodiments, a nuclear tethered lncRNA comprises PINCR lncRNA. In some embodiments, a nuclear tethered lncRNA comprises MANTIS lncRNA. In some embodiments, a nuclear tethered lncRNA comprises LncPRESS1 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises HAND2-AS lncRNA. In some embodiments, a nuclear tethered lncRNA comprises HOTAIR lncRNA. In some embodiments, a nuclear tethered lncRNA comprises HOTTIP lncRNA. In some embodiments, a nuclear tethered lncRNA comprises Braveheart lncRNA. In some embodiments, a nuclear tethered lncRNA comprises Fendrr lncRNA. In some embodiments, a nuclear tethered lncRNA comprises ANRIL lncRNA. In some embodiments, a nuclear tethered lncRNA comprises Chae lncRNA. In some embodiments, a nuclear tethered lncRNA comprises pRNA lncRNA. In some embodiments, a nuclear tethered lncRNA comprises Dum lncRNA. In some embodiments, a nuclear tethered lncRNA comprises PAPAS lncRNA. In some embodiments, a nuclear tethered lncRNA comprises Xist lncRNA. In some embodiments, a nuclear tethered lncRNA comprises Air lncRNA. In some embodiments, a nuclear tethered lncRNA comprises Dali lncRNA. In some embodiments, a nuclear tethered lncRNA comprises LincRNA-p21 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises CCND-Nat lncRNA. In some embodiments, a nuclear tethered lncRNA comprises MIAT lncRNA. In some embodiments, a nuclear tethered lncRNA comprises ecCEBPA lncRNA. In some embodiments, a nuclear tethered lncRNA comprises RMRP lncRNA. In some embodiments, a nuclear tethered lncRNA comprises PANDA lncRNA. In some embodiments, a nuclear tethered lncRNA comprises H19 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises TARID lncRNA. In some embodiments, a nuclear tethered lncRNA comprises SLERT lncRNA. In some embodiments, a nuclear tethered lncRNA comprises FIRRE lncRNA. In some embodiments, a nuclear tethered lncRNA comprises ANRASSF1 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises PARTICLE, APTR, or NEAT1_2 lncRNA. In some embodiments, a nuclear tethered lncRNA comprises NEAT1_2 lncRNA. [71] In some embodiments, a lncRNA condensate comprises PVT1 lncRNA. In some embodiments, a lncRNA condensate comprises KCNQ1OT1 lncRNA. In some embodiments, a lncRNA condensate comprises AIRN lncRNA. In some embodiments, a lncRNA condensate comprises PINT lncRNA. In some embodiments, a lncRNA condensate comprises Linc-Pint lncRNA. In some embodiments, a lncRNA condensate comprises MALAT1 lncRNA. In some embodiments, a lncRNA condensate comprises TERC lncRNA. In some embodiments, a lncRNA condensate comprises MEG3 lncRNA. In some embodiments, a lncRNA condensate comprises LINC00472 lncRNA. In some embodiments, a lncRNA condensate comprises TUG1 lncRNA. In some embodiments, a lncRNA condensate comprises KLRA1P lncRNA. In some embodiments, a lncRNA condensate comprises PINCR lncRNA. In some embodiments, a lncRNA condensate comprises MANTIS lncRNA. In some embodiments, a lncRNA condensate comprises LncPRESS1 lncRNA. In some embodiments, a lncRNA condensate comprises HAND2-AS lncRNA. In some embodiments, a lncRNA condensate comprises HOTAIR lncRNA. In some embodiments, a lncRNA condensate comprises HOTTIP lncRNA. In some embodiments, a lncRNA condensate comprises Braveheart lncRNA. In some embodiments, a lncRNA condensate comprises Fendrr lncRNA. In some embodiments, a lncRNA condensate comprises ANRIL lncRNA. In some embodiments, a lncRNA condensate comprises Chae lncRNA. In some embodiments, a lncRNA condensate comprises pRNA lncRNA. In some embodiments, a lncRNA condensate comprises Dum lncRNA. In some embodiments, a lncRNA condensate comprises PAPAS lncRNA. In some embodiments, a lncRNA condensate comprises Xist lncRNA. In some embodiments, a lncRNA condensate comprises Air lncRNA. In some embodiments, a lncRNA condensate comprises Dali lncRNA. In some embodiments, a lncRNA condensate comprises LincRNA-p21 lncRNA. In some embodiments, a lncRNA condensate comprises CCND-Nat lncRNA. In some embodiments, a lncRNA condensate comprises MIAT lncRNA. In some embodiments, a lncRNA condensate comprises ecCEBPA lncRNA. In some embodiments, a lncRNA condensate comprises RMRP lncRNA. In some embodiments, a lncRNA condensate comprises PANDA lncRNA. In some embodiments, a lncRNA condensate comprises H19 lncRNA. In some embodiments, a lncRNA condensate comprises TARID lncRNA. In some embodiments, a lncRNA condensate comprises SLERT lncRNA. In some embodiments, a lncRNA condensate comprises FIRRE lncRNA. In some embodiments, a lncRNA condensate comprises ANRASSF1 lncRNA. In some embodiments, a lncRNA condensate comprises PARTICLE, APTR, or NEAT1_2 lncRNA. In some embodiments, a lncRNA condensate comprises NEAT1_2 lncRNA. [72] Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the methods of use described herein pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the methods of use, exemplary methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting. Each literature reference or other citation referred to herein is incorporated herein by reference in its entirety. [73] As used herein, the terms “comprise”, "comprises", "comprising", "includes", "including", “having” and their conjugates mean "including but not limited to". [74] As used herein, the term “consisting of” means “including and limited to”. [75] As used herein, the term "consisting essentially of" means that the composition, method or structure may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure. [76] As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "an enzyme" or "at least one enzyme" may include a plurality of enzymes, including mixtures thereof. [77] As used herein the term "method" refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts. [78] As used herein, the terms “treat”, “treating”, “treatment”, or “therapy” (as well as different forms thereof) refer to therapeutic treatment, including prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) an undesired physiological change associated with a disease or condition. Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of the extent of a disease or condition, stabilization of a disease or condition (i.e., where the disease or condition does not worsen), delay or slowing of the progression of a disease or condition, amelioration or palliation of the disease or condition, and remission (whether partial or total) of the disease or condition, whether detectable or undetectable. Those in need of treatment include those already with the disease or condition as well as those prone to having the disease or condition or those in which the disease or condition is to be prevented. [79] Pharmaceutical compositions suitable for use in the methods disclosed herein include compositions wherein the active ingredients are contained in an amount effective to achieve the intended purpose. More specifically, a therapeutically effective amount means an amount of active ingredients effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated. Determination of a therapeutically effective amount is well within the capability of those skilled in the art. [80] A skilled artisan would appreciate that the terms “composition” and “pharmaceutical composition” may in some embodiments, be used interchangeably having all the same qualities and meanings. In some embodiments, disclosed herein is a pharmaceutical composition for use in methods identifying a treatment agent for a subject suffering from a condition or disease associated with a lncRNA. In some embodiments, disclosed herein is a pharmaceutical composition comprising a small molecule as described herein, for the use in methods identifying a treatment agent for a subject suffering from for treating a condition or disease associated with a lncRNA. In some embodiments, disclosed herein is a pharmaceutical composition for use in methods of treatment of a condition or disease associated with a lncRNA. In some embodiments, disclosed herein is a pharmaceutical composition comprising a small molecule as described herein, use in methods for treating a condition or disease associated with a lncRNA. [81] In some embodiments, a pharmaceutical composition comprises a small molecule. In some embodiments, a pharmaceutical composition comprises a small molecule comprising an inhibitor of DNA topoisomerase II. In some embodiments, an inhibitor of DNA topoisomerase II comprises an anthracycline drug. In some embodiments, an inhibitor of DNA topoisomerase II comprises Doxorubicin or Etoposide. In some embodiments, a pharmaceutical composition comprises Actinomycin D (ActD). In some embodiments, a pharmaceutical composition comprises Doxorubicin. In some embodiments, a pharmaceutical composition comprises Mithramycin A. In some embodiments, a pharmaceutical composition comprises Mitomycin. In some embodiments, a pharmaceutical composition comprises Mitoxantrone. In some embodiments, a pharmaceutical composition comprises Etoposide. In some embodiments, a pharmaceutical composition comprises Flavopriridol. [82] In some embodiments, for any preparation used in the methods disclosed herein, the therapeutically effective amount or dose can be estimated initially from in vitro assays. For example, a dose can be formulated in animal models and such information can be used to more accurately determine useful doses in humans. In another embodiment, toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, in cell cultures or experimental animals. The data obtained from these in vitro and cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage may vary depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. [83] In some embodiments, methods disclosed herein for treating lncRNA condensate associated human diseases or conditions comprises administering to a subject in need a therapeutically effective amount of a small molecule that binds to double stranded DNA (dsDNA), thereby treating the human disease or condition. In some embodiments, methods disclosed herein for treating lncRNA condensate associated human diseases or conditions comprises administering to a subject in need a therapeutically effective amount of a small molecule that binds to the minor groove of dsDNA, thereby treating the human disease or condition. In some embodiments, methods disclosed herein for treating lncRNA condensate associated human diseases or conditions comprises administering to a subject in need a therapeutically effective amount of a small molecule that binds to the minor groove and a major groove of dsDNA, thereby treating the human disease or condition. In some embodiments, methods disclosed herein for treating lncRNA condensate associated human diseases or conditions comprises administering to a subject in need a therapeutically effective amount of a small molecule that binds by intercalating with dsDNA, thereby treating the human disease or condition. [84] In some embodiments, the in vitro methods disclosed herein for identifying a treatment agent for a subject suffering from a lncRNA condensate associated human diseases or conditions comprises culturing cells of a biological sample with a small molecule that binds to dsDNA. In some embodiments, a small molecule binds to the minor groove of dsDNA. In some embodiments, a small molecule binds to the minor groove and a major groove of dsDNA. In some embodiments, a small molecule binds by intercalating with dsDNA, thereby treating the human disease or condition. [85] In some embodiments of methods disclosed herein, binding of the small molecule to DNA disrupts RNA-dsDNA triple helix structures. In some embodiments, binding of the small molecule to DNA disrupts lncRNA-dsDNA triple helix structures. In some embodiments, binding of the small molecule to DNA disrupts membraneless organelle-dsDNA triple helix structures. In some embodiments, binding of the small molecule to DNA disrupts paraspeckle structures. In some embodiments, binding of the small molecule to DNA disrupts a ribonucleoprotein complex. [86] In some embodiments of methods disclosed herein, binding of the small molecule to DNA disintegrates lncRNA-dsDNA triple helix structures. In some embodiments, binding of the small molecule to DNA disintegrates lncRNA-dsDNA triple helix structures. In some embodiments, binding of the small molecule to DNA disintegrates membraneless organelle-dsDNA triple helix structures. In some embodiments, binding of the small molecule to DNA disintegrates paraspeckle structures. In some embodiments, binding of the small molecule to DNA disintegrates a ribonucleoprotein complex. [87] In some embodiments of methods disclosed herein, binding of the small molecule to DNA disrupts and disintegrates RNA-dsDNA triple helix structures. In some embodiments, binding of the small molecule to DNA disrupts and disintegrates lncRNA-dsDNA triple helix structures. In some embodiments, lncRNA-dsDNA triple helix structures comprises lncRNA condensates. In some embodiments, lncRNA-dsDNA triple helix structures comprises paraspeckles. In some embodiments, binding of the small molecule to DNA disrupts and disintegrates membraneless organelle-dsDNA triple helix structures. In some embodiments, binding of the small molecule to DNA disrupts and disintegrates paraspeckle structures. In some embodiments, binding of the small molecule to DNA disrupts and disintegrates a ribonucleoprotein complex. [88] In some embodiments, disruption comprises a partial disruption of a RNA-dsDNA triple helix structure. In some embodiments, disruption comprises a complete disruption of a RNA- dsDNA triple helix structure. In some embodiments, disruption comprises a partial disruption of a lncRNA condensate. In some embodiments, disruption comprises a complete disruption of a lncRNA condensate. In some embodiments, disruption comprises a partial disruption of a paraspeckle. In some embodiments, disruption comprises a complete disruption of a paraspeckles. In some embodiments, disruption comprises a partial disruption of a membraneless organelle structure. In some embodiments, disruption comprises a complete disruption of a membraneless organelle structure. In some embodiments, disruption comprises a partial disruption of a ribonucleoprotein complex. In some embodiments, disruption comprises a complete disruption of a ribonucleoprotein complex. [89] In some embodiments, disintegration comprises a partial disintegration of a RNA-dsDNA triple helix structure. In some embodiments, disintegration comprises a complete disintegration of a RNA-dsDNA triple helix structure. In some embodiments, disintegration comprises a partial disintegration of a lncRNA condensate. In some embodiments, disintegration comprises a complete disintegration of a lncRNA condensate. In some embodiments, disintegration comprises a partial disintegration of a paraspeckle. In some embodiments, disintegration comprises a complete disintegration of a paraspeckles. In some embodiments, disintegration comprises a partial disintegration of a membraneless organelle structure. In some embodiments, disintegration comprises a complete disintegration of a membraneless organelle structure. In some embodiments, disintegration comprises a partial disintegration of a ribonucleoprotein complex. In some embodiments, disintegration comprises a complete disintegration of a ribonucleoprotein complex. [90] In some embodiments of a method disclosed herein, binding of the small molecule is under physiological conditions. In some embodiments, for example for methods of treatment discloses herein, binding comprises in vivo binding. In some embodiments, for example methods of identifying a treatment agent, binding comprises in vitro binding. [91] In some embodiments of methods disclosed herein, binding comprises non-sequence specific binding. In some embodiments of methods disclosed herein, binding comprises structural specific binding. In some embodiments of methods disclosed herein, binding comprises binding that does not inhibit RNA transcription. In some embodiments of methods disclosed herein, binding comprises binding that introduces a double strand break in the DNA. In some embodiments of methods disclosed herein, binding comprises any combination of non-sequence specific binding, structurally specific DNA binding, not inhibiting RNA transcription, and introducing a double strand break in the DNA. [92] A skilled artisan would recognize that the terms “DNA” and “dsDNA” may in some embodiments be used interchangeably having all the same meanings and qualities. [93] A skilled artisan would appreciate that small molecules that bind to dsDNA may encompass a family of small molecules that are binding to a nucleic acid in a non-intercalating mode or by intercalating. In some, the small molecule described herein bind the minor groove in dsDNA. In some, the small molecule described herein bind the minor groove and the major in dsDNA. In some, the small molecule described herein binds by intercalating with dsDNA. In some, the small molecule described herein binds but does not intercalate with dsDNA. [94] In some embodiments, minor groove binding molecules comprise molecules that selectively bind non-covalently to the minor groove of dsDNA, a shallow furrow in the dsDNA helix. In some embodiments, a small molecule used in a method disclosed herein and which binds the minor groove of dsDNA is a natural compound. In some embodiments, a small molecule used in a method disclosed herein and which binds the minor groove of dsDNA is a synthetic compound. In some embodiments, a small molecule used in the methods disclosed herein binds to A-T rich sequences in the dsDNA. In some embodiments, a small molecule used in the methods disclosed herein binds independent of the specific sequence in the dsDNA. In some embodiments, a small molecule used in the methods disclosed herein binds non-covalently to the minor groove of dsDNA. In some embodiments, a small molecule used in the methods disclosed herein binds hydrophobically with dsDNA. [95] A skilled artisan would recognize that the terms “small molecules”, “molecules”, “treatment agent”, and “binder”, and grammatical versions thereof, may be used interchangeable having all the same meanings and qualities, and encompass the small molecules described herein that bind DNA. [96] In some embodiments, minor groove and major groove binding molecules comprise molecules that selectively bind non-covalently to the minor and major groove of dsDNA, a shallow furrow in the DNA helix. In some embodiments, a small molecule used in a method disclosed herein and which binds the minor and major groove of dsDNA is a natural compound. In some embodiments, a small molecule used in a method disclosed herein and which binds the minor and major groove of dsDNA is a synthetic compound. In some embodiments, a small molecule used in the methods disclosed herein that binds to the minor and major groove binds to A-T rich sequences in the dsDNA. In some embodiments, a small molecule used in the methods disclosed herein that binds to the minor and major groove, binds independent of the specific sequence in the dsDNA. In some embodiments, a small molecule used in the methods disclosed herein binds non-covalently to the minor and major groove of dsDNA. In some embodiments, a small molecule used in the methods disclosed herein that binds to the minor and major groove, binds hydrophobically with dsDNA. [97] In some embodiments, binding molecules comprise molecules that selectively intercalate with dsDNA, thereby binding non-covalently to the dsDNA. In some embodiments, a small molecule used in a method disclosed herein that intercalates with dsDNA, is a natural compound. In some embodiments, a small molecule used in a method disclosed herein that intercalates with dsDNA, is a synthetic compound. In some embodiments, a small molecule used in a method disclosed herein that intercalates with dsDNA, intercalates non-covalently within the planer bases of the dsDNA. In some embodiments, a small molecule used in a method disclosed herein that intercalates with dsDNA, may interact hydrophobically with dsDNA. [98] In some embodiments of the methods disclosed herein for identifying a treatment agent for a human subject suffering from a disease associated with lncRNA, a small molecule that binds dsDNA comprises a chemotherapeutic agent. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA, a small molecule that binds dsDNA comprises a chemotherapeutic agent. [99] DNA minor groove binders comprising chemotherapeutic agents may in some embodiments comprise small molecules that cause permanent DNA damage. In some embodiments of the methods disclosed herein for identification of a treatment agent for a human subject suffering from a disease associated with lncRNA, a small molecule that binds the minor groove comprises a chemotherapeutic agent. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA, a small molecule that binds the minor groove comprises a chemotherapeutic agent. In some embodiments of the methods disclosed herein for identification of a treatment agent for a human subject suffering from a disease associated with lncRNA, a binder comprises small molecules that interact with the DNA and cause inhibition of DNA-dependent functions. DNA minor groove binders comprising chemotherapeutic agents may in some embodiments comprise small molecules that interact with the DNA and cause inhibition of DNA-dependent functions.. [100] \ DNA minor and major groove binders comprising chemotherapeutic agents may in some embodiments comprise small molecules that cause permanent DNA damage. In some embodiments of the methods disclosed herein for identification of a treatment agent for a human subject suffering from a disease associated with lncRNA, a small molecule that binds the minor and major groove comprises a chemotherapeutic agent. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA, a small molecule that binds the minor and major groove comprises a chemotherapeutic agent. In some embodiments of the methods disclosed herein for identification of a treatment agent for a human subject suffering from a disease associated with lncRNA, a binder comprises small molecules that binds both the minor and major groove of dsDNA and interacts with the DNA, causes inhibition of a DNA-dependent function. DNA minor and major groove binders comprising chemotherapeutic agents may in some embodiments comprise small molecules that interact with the dsDNA and cause inhibition of DNA-dependent functions. [101] In some embodiments of methods disclosed herein, the binding small molecule intercalates with the dsDNA. In some embodiments, small molecules that intercalate comprise a chemotherapeutic agent. In some embodiments, small molecules that intercalate cause inhibition of a DNA-dependent functions. [102] In some embodiments, dsDNA minor groove binding molecules comprising chemotherapeutic agents may in some embodiments comprise small molecules that interact with the DNA and do not cause significant structural changes in the dsDNA. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA, a small molecule that binds the dsDNA minor groove comprises a chemotherapeutic agent. dsDNA small molecule minor groove binders comprising chemotherapeutic agents may in some embodiments comprise small molecules that arrest cell cycle. [103] dsDNA minor and major groove binders comprising chemotherapeutic agents may in some embodiments comprise small molecules that interact with the dsDNA and do not cause significant structural changes in the dsDNA. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA, a small molecule that binds the minor and major groove comprises a chemotherapeutic agent. DNA minor and major groove binders comprising chemotherapeutic agents may in some embodiments comprise small molecules that arrest cell cycle. [104] Small molecules that intercalate with DNA, may in some embodiments comprise chemotherapeutic agents, wherein the interaction with dsDNA does not cause significant structural changes in the dsDNA. In some embodiments of the methods disclosed herein for identifying a treatment agent for a human subject suffering from a disease associated with lncRNA, a treatment agent intercalate with the dsDNA comprises a chemotherapeutic agent. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA, a small molecule that intercalate with the dsDNA comprises a chemotherapeutic agent. Intecalation binders comprising chemotherapeutic agents may in some embodiments comprise small molecules that arrest cell cycle. [105] In some embodiments of the methods disclosed herein for identifying a treatment agent for a human subject suffering a disease associated with lncRNA condensates, a small molecule that binds dsDNA comprises an inhibitor of DNA topoisomerase II. In some embodiments of the methods for identifying a treatment agent, an inhibitor of DNA topoisomerase II comprises Etoposide or Doxorubicin. In some embodiments of the methods disclosed herein for identifying a treatment agent for a human subject suffering a disease associated with lncRNA condensates, a small molecule that binds dsDNA comprises Actinomycin D (ActD), Doxorubicin, Mithramycin A, Mitomycin, Mitoxantrone, Etoposide, or Flavopriridol. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA condensates, a small molecule that binds dsDNA comprises an inhibitor of DNA topoisomerase II. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA condensates, a small molecule that binds dsDNA comprises an inhibitor of DNA topoisomerase II comprising Etoposide or Doxorubicin. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA condensates, a small molecule that binds dsDNA comprises Actinomycin D (ActD), Doxorubicin, Mithramycin A, Mitomycin, Mitoxantrone, Etoposide, or Flavopriridol. [106] A skilled artisan would appreciate that current knowledge in the art discloses the Doxorubicin intercalates in dsDNA, Actinomycin D binds to the minor groove of dsDNA, Mithramycin binds to the minor groove of dsDNA, Mitomycin binds to the minor groove of dsDNA, Hoechst binds to minor groove of dsDNA, Etoposide binds both the minor and major groove of dsDNA, Mitoxantrone intercalates within dsDNA, and it is thought that Flavopiridol intercalates within dsDNA. A skilled artisan would appreciate that inhibitors of DNA topoisomerase II include anthracycline drugs, which intercalate in dsDNA and may also interfere with DNA metabolism and RNA production. In some embodiments, a small molecule used in a method of treatment herein, comprises an anthracycline drug. In some embodiments, treatment agents identified comprise small molecules comprising anthracycline drugs. [107] In some embodiments, binding of the small molecule introduces a double strand break in the DNA. In some embodiments, binding disintegrates or disrupts or a combination thereof, a paraspeckle condensates comprising a lncRNA. In some embodiments, binding disintegrates or disrupts or a combination thereof, a membraneless organelle comprising a lncRNA. In some embodiments, binding disintegrates or disrupts or a combination thereof, a nucleoprotein complex comprising a lncRNA. In some embodiments, binding degrades a lncRNA condensates. In some embodiments, binding degrades a paraspeckle. In some embodiments, binding degrades a membraneless organelle comprising a lncRNA. In some embodiments, binding degrades a nucleoprotein complex comprising a lncRNA. In some embodiments, binding completely degrades a lncRNA condensates. In some embodiments, binding completely degrades paraspeckle. In some embodiments, binding completely degrades a membraneless organelle comprising a lncRNA. In some embodiments, binding completely degrades a nucleoprotein complex comprising a lncRNA. A skilled artisan would appreciate that method to measure double strand breaks and observe disintegration or disruption or degradation of lncRNA condensates, including paraspeckles, membraneless organelles, and ribonucleoprotein complexes are well known in the art, and are exemplified in the Examples below. [108] In some embodiments, binding of a small molecule that binds dsDNA disintegrates a lncRNA condensates. In some embodiments, binding of a small molecule that binds dsDNA disintegrates a paraspeckle. In some embodiments, binding of a small molecule that binds dsDNA degrades a lncRNA. In some embodiments, binding of a small molecule that binds dsDNA degrades a paraspeckles. In some embodiments, binding of a small molecule that binds dsDNA disintegrates a lncRNA condensate. In some embodiments, binding of a small molecule that binds dsDNA disintegrates a paraspeckle. [109] In some embodiments, binding of a small molecule that binds dsDNA disrupts a lncRNA condensate. In some embodiments, binding of a small molecule that binds dsDNA disrupts a paraspeckle. In some embodiments, binding of a small molecule that binds dsDNA disrupts and disintegrates a lncRNA condensate. In some embodiments, binding of a small molecule that binds dsDNA disrupts and disintegrates a paraspeckle. [110] In some embodiments, binding of a small molecule that binds dsDNA disrupts a membraneless organelle comprising a lncRNA. In some embodiments, binding of a small molecule that binds dsDNA disrupts a ribonucleoprotein complex comprising a lncRNA. In some embodiments, binding of a small molecule that binds dsDNA disrupts and disintegrates a membraneless organelle comprising a lncRNA. In some embodiments, binding of a small molecule that binds dsDNA disrupts and disintegrates a ribonucleoprotein complex comprising a lncRNA. [111] In some embodiments, disruption, disintegration, or degradation of a lncRNA condensate leads to an absence of lncRNA condensates. In some embodiments, disruption or degradation of a lncRNA condensate leads to a decrease of lncRNA condensates. In some embodiments, disruption of a paraspeckle comprises small speckle formation. In some embodiments, disruption of a paraspeckle leads to an absence of paraspeckles or small speckles. In some embodiments, degradation of a paraspeckle comprises an absence of paraspeckles or speckles. In some embodiments, disintegration of a paraspeckle comprises small speckle formation. In some embodiments, degradation of a paraspeckle comprises small speckle formation. In some embodiments, disintegration of a paraspeckle leads to an absence of paraspeckles or small speckles. In some embodiments, disruption and disintegration of a paraspeckle comprises small speckle formation. In some embodiments, disruption and disintegration of a paraspeckle leads to an absence of paraspeckles or small speckles. In some embodiments, disruption, disintegration, or degradation of a membraneless organelle leads to an absence of membraneless organelles. In some embodiments, disruption or degradation of a membraneless organelle leads to a decrease of membraneless organelles. In some embodiments, disruption, disintegration, or degradation of a ribonucleoprotein complex leads to an absence of ribonucleoprotein complexes. In some embodiments, disruption or degradation of a ribonucleoprotein complex leads to a decrease of ribonucleoprotein complexes. [112] In some embodiments of the methods disclosed herein for identifying a treatment agent for a subject suffering from a disease associated with lncRNA condensate, the lncRNA condensate comprises any lncRNA known in the art and disclosed in LncRNA databases as being associated with a human disease or condition. In some embodiments of the methods disclosed herein for identifying a treatment agent for a subject suffering from a disease associated with a lncRNA condensate, the lncRNA comprises of PVT1, KCNQ1OT1, AIRN, PINT, Linc-Pint, MALAT1, TERC, MEG3, LINC00472, TUG1, KLRA1P, PINCR, MANTIS, LncPRESS1, HAND2-AS, HOTAIR, HOTTIP, Braveheart, Fendrr, ANRIL, Chaer, pRNA, Dum, PAPAS, Xist, Air, Dali, LincRNA-p21, CCND-Nat, MIAT, ecCEBPA, RMRP, PANDA, H19, TARID, SLERT, FIRRE, ANRASSF1, PARTICLE, APTR, NEAT1_2, or any combination thereof. [113] In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA condensate, the lncRNA condensate comprises any lncRNA known in the art and disclosed in LncRNA databases as being associated with a human disease or condition. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA condensates, the lncRNA comprises of PVT1, KCNQ1OT1, AIRN, PINT, Linc-Pint, MALAT1, TERC, MEG3, LINC00472, TUG1, KLRA1P, PINCR, MANTIS, LncPRESS1, HAND2-AS, HOTAIR, HOTTIP, Braveheart, Fendrr, ANRIL, Chaer, pRNA, Dum, PAPAS, Xist, Air, Dali, LincRNA-p21, CCND-Nat, MIAT, ecCEBPA, RMRP, PANDA, H19, TARID, SLERT, FIRRE, ANRASSF1, PARTICLE, APTR, NEAT1_2, or any combination thereof. [114] In some embodiments of the methods disclosed herein for identifying a treatment agent for a subject suffering from a disease associated with lncRNA condensate, the human disease or condition comprises a cancer, a neurological disease, an autoimmune disease, or a cardiac disease or condition. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA condensates, the human disease or condition comprises a cancer, a neurological disease, an autoimmune disease, or a cardiac disease or condition. [115] In some embodiments of methods described herein, a cancer comprises lymphoblastic a leukemia, acute myeloblastic leukemia, Wilms’ tumor, neuroblastoma, soft tissue and bone sarcomas, breast carcinoma, ovarian carcinoma, transitional cell bladder carcinoma, thyroid carcinoma, gastric carcinoma, Hodgkin’s disease, a lymphoma, a non-lymphocytic leukemia, and glioblastoma multiforme, childhood rhabdomyosarcoma, Ewing's sarcoma and metastatic, testicular cancer, non-seminomatous testicular cancer, esophageal cancer, leukemia (lymphoid), lung cancer, liver cancer, malignant lymphoma and bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. In some embodiments of methods described herein, a cancer comprises a malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, or urinary bladder, or any combination thereof. [116] In some embodiments of methods described herein, a cancer comprises axillary lymph node involvement following resection of primary breast cancer. In some embodiments of methods described herein, a cancer comprises a pre-cancerous condition. In some embodiments of methods described herein, a cancer comprises a malignancy of a cancer. In some embodiments of methods described herein, a cancer comprises hypercalcemia and hypercalciuria associated with a variety of advanced forms of cancer. In some embodiments of methods described herein, a cancer comprises a refractory testicular tumor. [117] In some embodiments of the methods disclosed herein, for identifying a treatment agent for a human suffering from a disease associated with lncRNA condensates, a neurological disease or condition comprises schizophrenia, bipolar disorder, cerebral ischemia, frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple system atrophy, spinal muscular atrophy, multiple sclerosis, Cerebral Palsy, Autism Spectrum Disorder, Epilepsy or Huntington’s disease. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA condensates, a neurological disease or condition comprises schizophrenia, bipolar disorder, cerebral ischemia, frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple system atrophy, spinal muscular atrophy, multiple sclerosis, Cerebral Palsy, Autism Spectrum Disorder, Epilepsy or Huntington’s disease. [118] A skilled artisan would appreciate that neurological diseases or conditions may be characterized by dysfunction associated with loss of neural cells in the brain and/or spinal cord. Acute neurodegeneration may result from a temporally discrete insult, such as stroke or trauma, leading to a localized loss of neurons at the site of injury. Chronic neurodegeneration may develop over a long period of time and results in the loss of a particular neuronal subtype or generalized loss of neuronal populations. [119] In some embodiments of the methods disclosed herein, for identifying a treatment agent for a human suffering from a disease associated with lncRNA condensates, an autoimmune disease comprises diabetes. In some embodiments of the methods disclosed herein for treating a disease associated with lncRNA condensates, an autoimmune disease comprises diabetes. [120] A skilled artisan would appreciate that in some embodiments, it may be possible to identify a target agent that is known in the art, wherein the method of identifying the target agent described herein in details, leads to the ability to treat a specific disease or groups of disease. For example, in certain methods of use disclosed herein a human disease or condition comprises a cancer and ActD is identified as a treatment agent for said subject, wherein said method of identifying comprises a further treating step comprising administering to the subject a therapeutically effective amount of a composition comprising ActD, thereby treating the human disease or condition. In some embodiments of methods disclosed herein wherein the treatment agent identifies comprises ActD, the cancer comprises of a Wilms' tumor, a childhood rhabdomyosarcoma, a Ewing's sarcoma or metastatic growth thereof, a non-seminomatous testicular cancer. In some embodiments, wherein said treating comprises use of an ActD composition, treating may encompass a combination chemotherapy and/or multi-modality treatment regimen. [121] In some embodiments, when said human disease or condition comprises a cancer and Doxorubicin is identified as a treatment agent for said subject, said method comprises a further treating step comprising administering to the subject a therapeutically effective amount of a composition comprising Doxorubicin, thereby treating the human disease or condition. In some embodiments, when Doxorubicin is identified and or used as a treatment agent, said cancer comprises a lymphoblastic leukemia, an acute myeloblastic leukemia, a Wilms’ tumor, neuroblastoma, a soft tissue and bone sarcoma, a breast carcinoma, an ovarian carcinoma, a transitional cell bladder carcinoma, a thyroid carcinoma, a gastric carcinoma, a Hodgkin’s disease, a malignant lymphoma or a bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. In some embodiments, said subject is female and said cancer comprises axillary lymph node involvement following resection of primary breast cancer, and said treating comprises an adjuvant therapy. [122] In some embodiments, when said human disease or condition comprises a cancer and Mithramycin A is identified as a treatment agent for said subject, said method comprises a further treating step comprising administering to the subject a therapeutically effective amount of a composition comprising Mithramycin, thereby treating the human disease or condition. In some embodiments, when Mithramycin A is identified and or used in methods disclosed herein, the cancer comprises testicular cancer, or hypercalcemia and hypercalciuria associated with an advanced forms of a cancer. [123] In some embodiments, when said human disease or condition comprises a cancer and Mitomycin is identified as a treatment agent for said subject, said method comprises a further treating step comprising administering to the subject a therapeutically effective amount of a composition comprising Mitomycin, thereby treating the human disease or condition. In some embodiments, wherein Mitomycin is identified and or used in said methods disclosed herein, said cancer comprises a malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, or urinary bladder. [124] In some embodiments, when said human disease or condition comprises a cancer and Etoposide is identified as a treatment agent for said subject, said method comprises a further treating step comprising administering to the subject a therapeutically effective amount of a composition comprising Etoposide, thereby treating the human disease or condition. In some embodiments, when Etoposide is identified and or used in methods disclosed herein, said cancer comprises a lymphoma, a non-lymphocytic leukemia, small cell lung cancer, or a glioblastoma multiforme, or said treating is used in combination with other chemotherapeutic agents and said cancer comprises refractory testicular tumors. [125] In some embodiments, when said human disease or condition comprises a neurological disease or condition and Mitoxantrone is identified as a treatment agent for said subject, said method comprises a further treating step comprising administering to the subject a therapeutically effective amount of a composition comprising Mitoxantrone, thereby treating the human disease or condition. In some embodiments, wherein Mitoxantrone is identified and or used in said methods disclosed herein, said neurological disease comprises secondary (chronic) progressive multiple sclerosis, a progressive relapsing multiple sclerosis, or a worsening relapsing-remitting multiple sclerosis. [126] In some embodiments, when said human disease or condition comprises a cancer and Flavorpiridol is identified as a treatment agent for said subject, said method comprises a further treating step comprising administering to the subject a therapeutically effective amount of a composition comprising Flavorpiridol, thereby treating the human disease or condition. In some embodiments, when Flavorpiridol is identified or used in methods disclosed herein, said cancer comprises an esophageal cancer, a leukemia (lymphoid), a lung cancer, a liver cancer, or a lymphoma [127] In some embodiments of a method of treating a human disease or condition associated with lncRNA condensate, the method inhibits, reducing the symptoms of, ameliorates, or alleviates, or any combination thereof, said disease or condition in the subject. [128] In some embodiments, small molecules described herein may be used in methods of identifying a treatment agent for a subject suffering from a disease or condition associated with a long non-coding RNA condensate, which include among other structures paraspeckles. By characterizing the effect of the small molecule on lncRNA condensates, such as paraspeckle presentation and appearance in a subject suffering from a lncRNA condensate associated disease or condition, a trained professional could in certain embodiments, recognize that the small molecule could be an effective treatment agent of a lncRNA condensate associated disease or condition. [129] In certain embodiments, a method of identifying a treatment agent for a human subject suffering from a disease or condition associated with a long non-coding RNA (lncRNA) condensate, comprises (a) collecting a biological sample comprising cells from the subject suffering from said disease or conditions associated with a lncRNA condensate; (b) culturing a portion of said cells of said biological sample with a small molecule that binds to double stranded DNA (dsDNA) and culturing a control portion of said cells without said small molecule; (c) incubating said cultures under physiological conditions for a period of time; (d) measuring the number and size of the lncRNA condensates present in the portion of cells incubated with said small molecule with the control portion of cells; and (e) comparing the number and size of the lncRNA condensates present in both portions of said sample, and determining if the number or size or both of said lncRNA condensates is reduced in the sample incubated with the small molecule; wherein if the number or size or both of said lncRNA condensates is reduced in the sample incubated with the small molecule compared with the control, then the small molecule is identified as a treatment agent for said subject. In some embodiments of a method of identifying a treatment agent, the lncRNA condensates comprise paraspeckles. [130] In some embodiments of a method of identifying a treatment agent, a biological sample comprises urine, blood, a tissue biopsy, or a tumor tissue biopsy. In some embodiments, a tissue biopsy comprises brain tissue, heart tissue, liver tissue, lung tissue, skin tissue, or fat tissue, or a combination thereof. [131] Methods of culturing and incubating cells under physiological conditions are well known in the art and would be used in a method for identifying a small molecule treatment agent as described herein. In some embodiments, cells comprise a complete nucleus. In some embodiments, cells comprise an intact nucleus. In some embodiments, cells comprise peripheral blood mononuclear cells (PBMC), adult fibroblasts, neonatal fibroblasts, neural crest cells, mesenchymal stem cells, adipocytes, myotubes, nephron progenitor cells, nephrons, osteocytes, cardiomyocytes, lung progenitor cells, hepatocytes, neural stem cells, motor neurons, astrocytes, cortical neuron progenitor cells, cortical neurons, neural stem cells, keratinocytes, trophoblast progenitor cells, endoderm cells, mesoderm cells, or any combination thereof. [132] In some embodiments, cells comprise adult fibroblasts. In some embodiments, cells comprise neonatal fibroblasts. In some embodiments, cells comprise peripheral blood mononuclear cell (PBMC). In some embodiments, cells comprise neural crest cells. In some embodiments, cells comprise mesenchymal stem cells. In some embodiments, cells comprise adipocytes. In some embodiments, cells comprise myotubes. In some embodiments, cells comprise nephron progenitor cells. In some embodiments, cells comprise nephrons. In some embodiments, cells comprise osteocytes. In some embodiments, cells comprise cardiomyocytes. In some embodiments, cells comprise lung progenitor cells. In some embodiments, cells comprise hepatocytes. In some embodiments, cells comprise neural stem cells. In some embodiments, cells comprise motor neurons. In some embodiments, cells comprise astrocytes. In some embodiments, cells comprise cortical neuron progenitor cells. In some embodiments, cells comprise cortical neurons. In some embodiments, cells comprise neural stem cells. In some embodiments, cells comprise keratinocytes. In some embodiments, cells comprise trophoblast progenitor cells. In some embodiments, cells comprise endoderm cells. In some embodiments, cells comprise mesoderm cells. [133] In some embodiments, cells comprise cancer cells. In some embodiments, cells comprise tumor cells. [134] In some embodiments, methods disclosed herein for identifying a treatment agent comprise a step of culturing cells with a small molecule that binds to dsDNA as disclosed herein, or a composition comprising the small molecule that binds to dsDNA, with the biological sample comprising cells, wherein said culture may then be observed for the presence of paraspeckles, speckles, or lncRNA condensates, or a combination thereof. In some embodiments, methods disclosed herein for identifying a treatment agent comprise a step of culturing cells with a small molecule that binds to dsDNA as disclosed herein, or a composition comprising the small molecule that binds to dsDNA, with the biological sample comprising cells, wherein said culture may then be observed for the presence of paraspeckles, speckles, or lncRNA condensates, or a combination thereof. In some embodiments, methods disclosed herein for identifying a treatment agent comprise a step of culturing cells with a small molecule that binds to the minor groove and the major groove of dsDNA as disclosed herein, or a composition comprising the small molecule that binds to dsDNA, with the biological sample comprising cells, wherein said culture may then be observed for the presence of paraspeckles, speckles, or lncRNA condensates, or a combination thereof. In some embodiments, methods disclosed herein for identifying a treatment agent comprise a step of culturing cells with a small molecule that binds to dsDNA as disclosed herein, or a composition comprising the small molecule that binds to dsDNA by intercalating with the DNA, with the biological sample comprising cells, wherein said culture may then be observed for the presence of paraspeckles, speckles, or lncRNA condensates, or a combination thereof. [135] In some embodiments of a methods of identifying a treatment agent, incubating comprises about 1-30 days. In some embodiments, incubating comprises about 1-15 days. In some embodiments, incubating comprises about 15-30 days. In some embodiments, incubating comprises about 1-5 days. In some embodiments, incubating comprises about 1-10 days. In some embodiments, incubating comprises about 1-2 days. In some embodiments, incubating comprises about 1-3days. In some embodiments, incubating comprises about 1-4 days. In some embodiments, incubating comprises about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 ,13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or30 days. [136] In some embodiments of a methods of identifying a treatment agent, incubating comprises about 1-5 weeks. In some embodiments of a methods of identifying a treatment agent, incubating comprises about 1, 2, 3, 4, or 5 weeks. EXAMPLES Example 1: Materials and Methods [137] PSC culture [138] Human embryonic stem cells (ESCs) of the H9 line (WiCELL Research Institute) and induced pluripotent stem cells (iPSCs) were cultured in StemMACS iPSBrew XF (Miltenyi Biotec) and passaged by StemMACS Passaging Solution (Miltenyi Biotec) on tissue culture- treated plates (Sigma) coated with Matrigel (ThermoFisher Scientific) diluted 1:100 in DMEM/F- 12 (ThermoFisher Scientific). All differentiation experiments were carried out with H9 cells, except lung progenitor and cortical neuron differentiations, which were performed with iPSC lines, namely NKX2.1-P2A-eGFP (R. Olmer, J. Dahlmann, S. Merkert, S. Baus, G. Göhring, and U. Martin, “Generation of a NKX2.1 knock-in reporter cell line from human induced pluripotent stem cells (MHHi006-A-2),” Stem Cell Research, vol. 39, p. 101492, Aug. 2019, doi: 10.1016/j.scr.2019.101492) and foreskin fibroblast-derived iPSCs (C. Kunze et al., “Synthetic AAV/CRISPR vectors for blocking HIV-1 expression in persistently infected astrocytes,” Glia, vol. 66, no. 2, pp. 413–427, 2018, doi: 10.1002/glia.23254), respectively. For paraspeckle measurements in trophoblast progenitors and neural crest cells, differentiation protocols were used, as previously described (C. Krendl et al., “GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency,” Proc. Natl. Acad. Sci. U.S.A., vol. 114, no. 45, pp. E9579–E9588, 072017, doi: 10.1073/pnas.1708341114; F. Matheus et al., “Pathological ASXL1 Mutations and Protein Variants Impair Neural Crest Development,” Stem Cell Reports, vol.12, no.5, pp.861–868, May 2019, doi: 10.1016/j.stemcr.2019.03.006), which are hereby incorporated in their entirety. [139] Fibroblast reprogramming [140] The reprogramming of human newborn dermal fibroblasts was performed using StemRNA 3rd Gen Reprogramming Kit (Reprocell) according to the manufacturer`s protocol. The RNA transfection cocktail included synthetic, non-modified RNA of reprogramming factors OCT4, SOX2, KLF4, cMYC, NANOG and LIN28A, immune evasion mRNAs of E3, K3, B18 and reprogramming-enhancing mature, double stranded microRNAs from the 302/367 cluster. 1.0x10⁴ fibroblasts were plated per 60 mm organ culture dish (Corning) and reprogramming was started the following day by lipofection of the mRNA cocktail and incubation overnight. Transfections were repeated daily for three days and at day 9, distinct iPSC colonies were forming. [141] Spontaneous differentiation [142] One day prior to beginning of spontaneous differentiation, 5.0x10⁵ cells that were dissociated using Accutase (Sigma) were transferred to one Matrigel-coated well of a 12-well plate with StemMACS iPSBrew XF and 10 μM Y-27632 (R&D Systems). After 24 h, medium was replaced with medium containing 20% KnockOut Serum Replacement (KSR), 1% GlutaMAX, 1% non-essential amino acids (NEAA) and 0.1 mM beta-Mercaptoethanol (all ThermoFisher Scientific). Fresh medium was applied daily for up to 3 days. [143] MSC, adipocyte, and osteocyte differentiation [144] Mesenchymal stem cell (MSC) differentiation was induced by exchanging StemMACS iPS-Brew XF medium with differentiation medium containing 20% KSR, 1% GlutaMAX, 1% NEAA and 0.1 mM beta-Mercaptoethanol supplemented with 10 μM SB431542 (Miltenyi Biotec). Fresh medium was applied every other day and after 7 days, cells were transferred in a 1:3 ratio to a non-coated tissue culture-treated plate with MSC expansion medium (Miltenyi Biotec). Fresh medium was applied daily before splitting the cells at differentiation day 14. Process control of MSC differentiation was performed by flow cytometry and RTqPCR at day 21. At day 21, MSCs were differentiated to adipocytes or osteocytes using StemMACS AdipoDiff Media or StemMACS OsteoDiff Media (both Miltenyi Biotec), respectively. Fresh medium was applied every 3 days for 20 days before process control by OilRed O or Alizarin Red staining, respectively. [145] Cardiomyocyte differentiation [146] Cardiomyocytes were generated according to a published protocol (X. Lian et al., “Directed cardiomyocyte differentiation from human pluripotent stem cells by modulating Wnt/β- catenin signaling under fully defined conditions,” Nat Protoc, vol. 8, no. 1, pp. 162–175, Jan. 2013, doi: 10.1038/nprot.2012.150, which is hereby incorporated in their entirety.). Briefly, 1.0x10⁶ cells were dissociated as single cells using Accutase and plated in a well of a 12-well plate with StemMACS iPSBrew XF and differentiation was induced the following day by changing the medium to RPMI-1640 (Sigma) with 2% B-27 supplement without Insulin (ThermoFisher Scientific) and 10 μM CHIR99021(R&D Systems). Same medium was used the following day and at day 3, half of the medium was replaced with RPMI/B-27 without insulin supplemented with 10 μM IWP-2 (Santa Cruz Biotechnology). At day 5 and 7, RPMI/B-27 first without insulin and then with full B-27 (ThermoFisher Scientific) were used. Fresh medium was applied after 3 days and cultures beginning to contract around day 12 were used for experiments. Process control of lateral mesoderm markers was performed at day 3. [147] Nephron differentiation [148] The protocol for differentiation of nephrons was optimized based on a published protocol (R. Morizane and J. V. Bonventre, “Generation of nephron progenitor cells and kidney organoids from human pluripotent stem cells,” Nat Protoc, vol. 12, no. 1, pp. 195–207, Jan. 2017, doi: 10.1038/nprot.2016.170, which is hereby incorporated in its entirety). Starting with undifferentiated cell cultures of ~70% confluency, a medium containing RPMI-1640, 1% GlutaMAX and 2% B-27 supplement (basal medium), 10 μM CHIR99021 and 500 nM dorsomorphin (Tocris) was used. Fresh medium was applied every other day and from day 4 onwards, the basal medium was supplemented with 10 ng/ml of Activin A (R&D Systems). At day 7, basal medium was supplemented with 10 ng/ml FGF9 (R&D Systems) and at day 9, with 3 μM CHIR99021 in addition for 48 h. Afterwards, basal medium supplemented with FGF9 was applied daily until day 21. Process controls were performed at day 7 for intermediate mesoderm markers, at day 14 for nephron progenitor markers and at day 21 for nephron markers by RT- qPCR and immunostaining. [149] Definitive endoderm, lung progenitor, and hepatocyte differentiation [150] The protocol for differentiation of definitive endoderm was based on a published protocol (M. Kajiwara et al., “Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells,” PNAS, vol. 109, no. 31, pp. 12538–12543, Jul. 2012, doi: 10.1073/pnas.1209979109, which is hereby incorporated in its entirety). Briefly, human pluripotent stem cells (hPSCs) were dissociated using Accutase and 4x10⁵ single cells were seeded in a Matrigel-coated 24-well in RPMI-1640 medium, supplemented with 2% B-27, 50 U/ml of penicillin/streptomycin (Pen/Strep; ThermoFisher Scientific), 100 ng/ml Activin A, 1 μM CHIR99021 and 10 μM Y-27632. Fresh medium was applied daily until day 6 without Y-27632, but with 0.25 mM sodium butyrate (Sigma) on the first day and 0.125 mM afterwards. Process controls were performed at day 6 by flow cytometry and RTqPCR. [151] Subsequent differentiation towards lung progenitor cells was based on a published protocol (S. Konishi et al., “Directed Induction of Functional Multi-ciliated Cells in Proximal Airway Epithelial Spheroids from Human Pluripotent Stem Cells,” Stem Cell Reports, vol.6, no. 1, pp. 18–25, Jan. 2016, doi: 10.1016/j.stemcr.2015.11.010, which is herein incorporated in its entirety). Briefly, foregut endoderm was induced using day 6 definitive endoderm cells by DMEM/F-12 medium, supplemented with 1% GlutaMAX, 2% B-27, 1% N-2 (ThermoFisher Scientific), 50 U/ml Pen/Strep, 0.05 mg/ml of L-ascorbic acid (Sigma), 0.4 mM of monothioglycerol (Sigma) (basal medium), 2 μM dorsomorphin and 10 μΜ SB431542. Fresh medium was applied daily and on day 10, lung progenitor differentiation was induced by applying basal medium supplemented with 20 ng/ml recombinant human BMP4 (R&D Systems), 50 nM retinoic acid (Sigma) and 3 μΜ CHIR99021. Fresh medium was applied daily until differentiation day 15 when expression of NKX2.1 was observed. [152] Hepatocyte differentiation was based on a published protocol (A. Carpentier et al., “Engrafted human stem cell-derived hepatocytes establish an infectious HCV murine model,” J. Clin. Invest., vol.124, no.11, pp.4953–4964, Nov.2014, doi: 10.1172/JCI75456, which is hereby incorporated in its entirety). Briefly, 1.5x10⁵ definitive endoderm cells were dissociated with Accutase, transferred to a Matrigel-coated 24-well and treated by DMEM/F-12 with 10% KSR, 1% NEAA, 1% GlutaMAX and DMSO (Sigma) together with 10 μM Y-27632 and 100 ng/ml recombinant human hepatocyte growth factor (R&D Systems). Medium was changed daily without Y-27632 for 10 days and process controls were conducted by RT-qPCR and immunofluorescence. [153] Neuronal Stem Cell Differentiation [154] The protocol for differentiation of neural stem cells (NSCs) was based on the generation of neurospheres (R. Morizane and J. V. Bonventre, “Generation of nephron progenitor cells and kidney organoids from human pluripotent stem cells,” Nat Protoc, vol. 12, no. 1, pp. 195–207, Jan. 2017, doi: 10.1038/nprot.2016.170, which is hereby incorporated in its entirety). Briefly, hESCs were harvested using a 2 mg/ml Collagenase IV solution (ThermoFisher Scientific) and resuspended in DMEM/F-12 medium supplemented with 20% KSR, 1% NEAA, 1% GlutaMAX, 10 μM SB431542, 5 μM dorsomorphin, 20 μM CHIR99021, 10 μM purmorphamine (Miltenyi Biotec) and 10 μM Y-27632, and plated on an ultra-low attachment 6-well (Corning). Fresh medium was applied without Y-27632. Forty-eight (48) h later, the basal medium was exchanged with N2B27-based medium containing a 1:1 mixture of DMEM-F-12 and Neurobasal A (ThermoFisher Scientific) with 0.5% N-2, 1% B-27 minus Vitamin A, 1% NEAA and 1% GlutaMAX, and the small molecules described above. At day 5, N2B27-based medium supplemented with 50 μg/ml L-ascorbic acid, SB431542 and dorsomorphin was applied. At day 7, the neurospheres were mechanically dissociated and plated on Matrigel-coated plates. Twenty- four (24) h before the replating, the medium was supplemented additionally with 5 ng/ml bFGF (Peprotech). Plated neurospheres were maintained for 7 days using the same medium and on day 14, confluent neuroepithelial outgrowths were passaged in a 1:10 dilution using Collagenase IV. The NSC cultures were passaged every 7 days and maintained in N2B27 medium with SB431542, dorsomorphin and bFGF at same concentrations as above with medium change every other day. Process control of NSC differentiation was performed at day 21. [155] Astrocyte differentiation [156] The protocol of astrocyte differentiation was based on a published protocol (A. Shaltouki, J. Peng, Q. Liu, M. S. Rao, and X. Zeng, “Efficient generation of astrocytes from human pluripotent stem cells in defined conditions,” Stem Cells, vol.31, no.5, pp.941–952, May 2013, doi: 10.1002/stem.1334, which is incorporated herein in its entirety). Briefly, tissue culture treated plates were coated for 2 h with 10 ng/ml laminin/poly-L-ornithine (Sigma) and day 21 NSCs were dissociated using Accutase, and plated at a ratio of 2.8x10⁵ cells per well of a 12-well plate with N2B27 medium supplemented with 20 ng/ml bFGF, 10 ng/ml BMP4 and 5 ng/ml CNTF (R&D Systems). On day 15, medium was supplemented with 10 ng/ml bFGF, 10 ng/ml EGF (Sigma) and 10 ng/ml Neuregulin (R&D Systems) and the cells were differentiated for additional 15 days and then analyzed. [157] Motor Neuron differentiation [158] The motor neuron differentiation was based on a published protocol (Q. Qu et al., “High- efficiency motor neuron differentiation from human pluripotent stem cells and the function of Islet-1,” Nature Communications, vol. 5, p. 3449, Mar. 2014, doi: 10.1038/ncomms4449, which is incorporated in its entirety). Briefly, plates were coated, first with 10 ng/ml laminin, poly-L- ornithine, collagen I and collagen IV (Sigma) for 1 h each and then with 10 ng/ml vitronectin (Peprotech) for 1 h. 10 ng/ml fibronectin (Sigma) instead of vitronectin was used for later passaging. 1.5x105 day 21 NSCs were seeded per well of a 12-well plate with N2B27 medium supplemented with 100 ng/ml SHH, 10 ng/ml BDNF, 10 ng/ml GDNF, 10 ng/ml IGF (all from R&D System) and 100 nM retinoic acid. After 15 days, the medium was supplemented with 0.1 μM ysecretase inhibitor XXI (Merck) and 0.1 μM cAMP (Sigma Aldrich). Cells were analyzed at day 75. [159] Cortical neuron differentiation [160] The protocol of cortical neuron differentiation was based on a previously published protocol (Y. Shi, P. Kirwan, and F. J. Livesey, “Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks,” Nat Protoc, vol.7, no.10, pp.1836–1846, Oct. 2012, doi: 10.1038/nprot.2012.116, which is incorporated herein in its entirety), with minor modifications. Briefly, iPSCs were plated in a 1:1 mixture of DMEM/F-12 and Neurobasal A, 1% N-2, 2% B-27, 1% GlutaMAX, 1% NEAA, 1000 U/mL Pen/Strep, 5 μg/ml human insulin (ThermoFisher Scientific) and 0.1 mM β-mercaptoethanol with 10 μM SB431542 and 1 μM dorsomorphin, and fresh media was applied daily. At day 10, cells were dissociated with Accutase and plated on poly-L-ornithine (1:1000) and laminin (1:200) coated plates at 1:4 dilution with the same medium supplemented with 10 μM Y-27632. From the next day onwards, the cells were treated by medium without SB431542 and dorsomorphin. Cells were passaged every six days. Process control for neural induction and cortical neuron progenitor differentiation was performed after 15 and 35 days. [161] Somatic cell lines [162] Somatic cell lines used in this study were GIBCO^® Human Skeletal myoblasts that were cultured for two days in DMEM (ThermoFisher Scientific) together with 2% horse serum (ThermoFisher Scientific), which induced differentiation to myotubes. Additionally, primary human epidermal keratinocytes (ATCC^® PCS200011^™), primary adult human dermal fibroblasts (ATCC^® PCS201012^™), primary human newborn foreskin fibroblasts (ATCC^® CRL-2522^™) and primary human astrocytes (ScienCellTM Research Laboratories, #1800) were cultured according to provider`s instructions. [163] Derivation of murine mesenchymal stem cells [164] Cultures of murine mesenchymal stem cells (MSCs) were established from the femoral bone marrow of female FVB/N mice (Charles River Laboratories, Sulzbach, Germany) by aspiration from the marrow cavity with 1 ml ice-cold PBS and a 0.4 mm injection needle. A solution of single cells was produced by pipetting, filtering through a 70 μm cell strainer (BD) and 5 min centrifugation at 300 g. Cells were plated in 12 ml of DMEM/F-12 with 1g/l glucose, 10% MSC-qualified FBS (ThermoFisher Scientific), 1% GlutaMAX and 10 μM Y-27632 in T75 cell culture flasks. Cells were kept under hypoxic conditions (2% O2, 5% CO2) at 37°C in a humidified atmosphere. Non-adherent cells were depleted by exchanging the medium 2 and 4 h after initial plating, whereas later on, fresh medium was applied every 3.5 days. When cells reached approximately 80% confluency, cells were passaged in a 1:3 ratio using Accutase. [165] Derivation of primary murine astrocytes [166] Primary mouse astrocytes of the C56BL/6 P3 strain were derived from whole cortex preparations. The brain was washed with HBSS (Sigma) supplemented with 50 U/ml Pen/Strep and meninges and blood vessels were removed. The cortex was isolated and cut into smaller pieces, and further resuspended in 10 ml HBSS/Pen/Strep. The minced tissue was plated on poly- D-lysine-coated plates (40 μg/ml, 1 h incubation) in DMEM/F-12 supplemented with 10% FBS, 50 U/ml Pen/Strep, 10 ng/ml FGF2 and10 ng/ml EGF. Fresh medium was applied every other day until the culture became confluent. [167] Derivation of primary murine cardiomyocytes [168] Primary mouse cardiomyocytes cultures were prepared using the Primary Cardiomyocyte Isolation kit (ThermoFisher Scientific) according to manufacturer`s instructions. [169] Derivation of primary murine hepatocytes [170] The protocol of primary hepatocyte derivation was based on a published protocol (L. A. Gonçalves, A. M. Vigário, and C. Penha-Gonçalves, “Improved isolation of murine hepatocytes for in vitro malaria liver stage studies,” Malaria Journal, vol. 6, no. 1, p. 169, Dec. 2007, doi: 10.1186/1475-2875-6-169, which is hereby incorporated in it entirety). Liver was obtained from 14 week old C56BL/6 mice and digested using 2 mg/ml collagenase IV solution (ThermoFisher Scientific) at 37ºC for 45 min. The digested tissue was plated in a 10 cm dish with Williams E medium (Sigma) supplemented with 5% FBS and mechanically dissociated. Then, cells were filtered using a 70 μm cell strainer and 6 ml cell suspension was layered on top of a Percoll (Sigma) gradient of 1.12 g/ml, 1.08 g/ml and 1.06 g/ml in PBS. Cells were centrifuged for 20 min at 800 g and washed with Williams E medium with 5% FBS. After another centrifugation at 300 g for 10 min, the cells were resuspended in Williams E medium with 5% FBS, 1% GlutaMAX, 50 U/ml Pen/Strep, 50 ng/ml EGF, 1 μg/ml Insulin, 10 μg/ml transferrin (Sigma), and 1.3 μg/ml of hydrocortisone (Sigma) and plated on 10 μg/ml rat tail collagen I (Sigma) coated plates with daily medium change. [171] Animal data [172] Mouse keeping was done at the central facilities at the Helmholtz Center Munich in accordance with the German animal welfare legislation and guidelines of the Society of Laboratory Animals (GV-SOLAS) and of the Federation of Laboratory Animal Science Associations (FELASA). [173] Oil Red O staining [174] Following adipocyte differentiation, cells were washed twice with PBS, fixed with 10% neutral buffered formalin (Sigma) for 45 min, then washed twice with tap water and fixed again with 2-propanol (Sigma) for 5 min. Filtered Oil Red O solution (1.8 mg/ml in 2-propanol; Sigma) was added to the cells and incubated for 10 min. After two washes with PBS, cells were counterstained with Mayer`s hematoxylin solution (Sigma) for 3 min, before two washes with tap water, addition of PBS and imaging with a phase-contrast microscope. All steps were performed at room temperature (RT). [175] Alizarin Red staining [176] Following osteocyte differentiations, cells were washed twice with PBS and fixed with 10% neutral buffered formalin (Sigma) for 45 min. Next, cells were washed twice with tap water and incubated with filtered alizarin red staining solution (20 mg/ml; Sigma) for 45 min. After 4 washes with de-ionized water, PBS was added to the cells and images were obtained with a phase- contrast microscope. All steps were performed at RT. [177] Immunofluorescence staining [178] Cells were grown on imaging slides (Ibidi), washed 3 times with PBS, fixed with 4% paraformaldehyde (Sigma) in PBS for 10 min, followed by 3 washes using PBS. After permeabilization using 0.5% Triton-X-100 (Sigma) in PBS at 4°C overnight and 3 washes with PBS, slides were blocked with 0.1% Triton-X-100 and 1% FBS in PBS for 1 h at room temperature. Incubation with primary antibodies was performed at 4°C overnight. After 3 washes with PBS, slides were incubated with the species corresponding secondary antibodies (ThermoFisher Scientific) for 2 h at room temperature in the dark and washed 3 times with PBS afterwards. The samples were mounted with ProLong^® Gold Antifade Reagent with DAPI (ThermoFisher Scientific) on a coverslip and imaged with an Axio Observer.Z1 inverted epifluorescence microscope (Zeiss) equipped with a 10x/0.3 Plan-NEOFLUAR objective (Zeiss). Primary antibodies were diluted 1:100 unless stated otherwise and secondary antibodies 1:1000 in blocking buffer. Primary antibodies that were used in this study are listed in the Table 1. [179] Table 1: Primary Antibodies

[180] Single molecule fluorescence in situ hybridization (smFISH) [181] Cells were plated on imaging slides (Ibidi), fixed with 4% paraformaldehyde, washed twice with PBS and permeabilized with 70% ethanol overnight at 4°C. After 2 washes with PBS and pre-hybridization solution (10% deionized formamide (Merck Millipore), 2x SSC), slides were incubated with 50 μl hybridization solution containing 2x SSC, 10% formamide, 50 μg competitor E.coli tRNA (Roche Diagnostics), 10% Dextrane Sulfate (VWR), 2 mg/ml BSA (UltraPure; Life Technologies), 10 mM vanadyl-ribonucleoside complex (NEB) and 1 ng/μl smFISH probes) for 6 h at 37°C. Afterwards, slides were washed twice with pre-hybridization solution at 37°C, then twice with PBS with subsequent mounting with ProLong^® Gold Antifade Reagent with DAPI. Slides were imaged after 12 hours when the mounting medium was fully cured on an Axio Observer.Z1 inverted epifluorescence microscope equipped with a 63x/1.4 Plan- APOCHROMAT objective (Zeiss). Probe Designer software by Biosearch Technologies was used to design probes for hNEAT15` segment and mNEAT1 middle segment, both conjugated to Quasar®670 fluorescent dye. Sequences are listed in SEQ ID NOs:1 and 2. [182] Table 2: NEAT1 smFISH probe Sequence

[183] Probes for hNEAT1 middle segment, mNEAT15` segment and MALAT1 (all conjugated to Quasar®570) were pre-designed by Biosearch Technologies. [184] Chemicals used for DNA binding [185] Cells were treated either by 2 μM Actinomycin D (ThermoFisher Scientific), 100 μg/ml Hoechst 33342 (ThermoFisher Scientific), 50 μM α-Amanitin (Cayman Chemical) and 5 μM Mithramycin A (Abcam). Vincristine (Selleckchem), Etoposide (Selleckchem) and Flavopiridol (Biomol) were used at concentrations specified in Figure 4F. [186] Image analysis for paraspeckle counting [187] The spot detection program Airlocalize (T. Trcek, T. Lionnet, H. Shroff, and R. Lehmann, “mRNA quantification using single-molecule FISH in Drosophila embryos,” Nat Protoc, vol.12, no. 7, pp. 1326–1348, Jul. 2017, doi: 10.1038/nprot.2017.030) was used for paraspeckle quantification based on 3D image stacks with 6 μm depth in 0.3 μm increments as described previously (18). The averaged number of paraspeckles was calculated from images containing 10- 150 cells. Seven (7) images were analyzed per condition and replicate. [188] Quantification of nucleus size [189] Quantification of nucleus size based on DAPI staining was done using the Fiji software. Per image, an intensity threshold was determined to mask the DAPI staining in a maximum projection of a 3D image stack with 6 μm depth. The total DAPI area was divided by the number of cells per image to determine the average nucleus size per cell per image. The determination of nuclear size in single cells (Figure 3B) was done by manually masking DAPI labelled nuclei and analyzing the nuclear area by the “Analyse Particles” function in Fiji. [190] Flow cytometry analysis [191] Surface marker staining was performed by washing dissociated cells with FACS buffer (1% FBS in PBS), centrifugation, removal of supernatant and incubation with primary antibodies in FACS buffer for 30 min on ice. Next, after centrifugation and removal of supernatant, cells were incubated with species corresponding secondary antibody for 30 min on ice, before washing and final resuspension in FACS buffer. A similar protocol was carried out with primary antibodies that were already conjugated to fluorophores. [192] Intracellular staining was performed according to instructions of the Inside Stain Kit (Miltenyi Biotec). Primary antibodies were incubated for 1 h at room temperature with 2.0x10⁵ cells. Secondary antibodies were incubated for 30 minutes on ice. Cells were washed once with Inside Perm solution before resuspending them in FACS buffer for analysis. [193] Unconjugated primary antibodies were diluted 1:100 and secondary antibodies 1:1000 in FACS buffer. Samples were analyzed using the BD FACSAria III cell sorter (BD Biosciences) and data was processed using FlowJo software. [194] RNA extraction and quantitative RT-PCR (RT-qPCR) [195] RNA extraction was performed using the RNeasy Mini Kit (Qiagen) according to manufacturer`s instructions. Reverse transcription was performed using the Verso cDNA Synthesis Kit (ThermoFisher Scientific) with 200 ng RNA per reaction. RT-qPCR was performed in 384-well plates using 5 μl of SYBR Green PCR Master Mix (ThermoFisher Scientific), 1 μl cDNA and 1 μl of 5 μM primer forward and reverse mix in a 10 μl reaction. PCR conditions were 2 min at 50°C and 10 min at 95°C followed by 40 cycles of 15 s at 95°C and 1 min at 60°C. Relative expression levels were calculated using the Delta-Delta Ct method normalized with GAPDH. Statistical analysis was performed with the GraphPad Prism 7 software. RT-qPCR primers are listed in Table 3. (SEQ ID NOs:3-156) [196] Table 3: RT-qPCR primers

[197] Generation of NEAT1-/-, NEAT1ΔTH and NEAT1STOP hESCs [198] Generation of NEAT1-/- and NEAT1ΔTH clones from human embryonic stem cells (hESCs) was carried out according to a published protocol (F. A. Ran, P. D. Hsu, J. Wright, V. Agarwala, D. A. Scott, and F. Zhang, “Genome engineering using the CRISPR-Cas9 system,” Nat Protoc, vol. 8, no. 11, pp. 2281–2308, Nov. 2013, doi: 10.1038/nprot.2013.143, which is incorporated herein in it entirety). Briefly, the Protospacer adjacent Motif (PAM) sequence was identified using the crispr.mit.edu website. BbsI-digested pSpCas9(BB)-2A-GFP vector (Addgene plasmid ID: 48138) was ligated with annealed forward/reverse guide RNA (gRNA) mix (1:250 dilution) using T4 ligase (NEB). NEB^® 5-alpha competent E.coli bacteria (NEB) were inoculated with ligated plasmid and plated on agar plates. Bacteria colonies were propagated, and plasmids were isolated using the GeneJET Plasmid MiniPrep kit (LifeTechnologies) according to manufacturer`s instructions. Sanger sequencing was used to screen correct integrations. 1.0x10⁶ hESCs were nucleofected with 5 μg of up- and downstream gRNA/Cas9 plasmid mix using the P3 Primary Cell 4D-Nucleofector^® Kit (Lonza) according to manufacturer`s instructions. Cells were plated 2 days later, and single clones were picked and analyzed for successful genomic deletion by PCR. NEAT1STOP hESCs were generated by inserting a polyA stop cassette approximately 1500 base pairs after the NEAT1 transcription start site. 1.0x10⁶ hESCs were transfected with 4 μg donor and 2 μg gRNA plasmid and clones were tested for successful integration by PCR. Guide RNAs and primers for PCR-based screening are listed in Tables 4A and 4B (SEQ ID NOs:157-165). [199] Tables 4A and 4B: Guide RNAs (4A) and Primers for PCR-based screening (4B)

[200] DNA extraction and Polymerase Chain reaction (PCR) [201] Isolation of genomic DNA for screening of KO clones after transfection of CRISPR/Cas9 was performed using 30 μl QuickExtractTM (Biozym) according to manufacturer`s instructions. PCR was performed using Q5 Polymerase mastermix (NEB) with 100 ng Example 2: Dynamics of nuclear lncRNAs in the differentiation of human PSCs [202] Objective: To conduct an unbiased assessment of the association of cell types and developmental stages with the expression and condensation of nuclear long non-coding RNAs (lncRNAs). [203] Results: In order to assess the association of cell types and developmental stages with the expression and condensation of lncRNAs, human pluripotent stem cells (PSCs) were differentiated to numerous lineages (Figure 1A). First, the differentiation protocols of lateral mesoderm and mesenchymal stem cells (MSCs), definitive endoderm and lung progenitor cells, and neural stem cells (NSCs) and cortical neuron progenitors were optimized, These differentiation protocols represent respectively, early and late stages of differentiation of the three germ layers mesoderm, endoderm and ectoderm. [204] Up-regulation was observed of lateral mesoderm markers MESP1, T (Brachyury), FZD4 and MIXL1, and transcription factors TWIST and SLUG, which regulate the epithelial-to- mesenchymal transition of MSCs, as well as surface markers that are characteristic for MSCs (Figure 1B and Figure 6A). When differentiated to definitive endoderm, the up-regulation of SOX17, FOXA2, surface markers CXCR4, CD117 and EPCAM, was detected and later of the master lung transcription factor NKX2.1 (Figure 1C and Figures 6B-D). Moreover, the upregulation of PAX6, SOX1, ASCL1, NESTIN and FOXG1 mRNAs and respective proteins confirmed the differentiation to NSCs and cortical neuron progenitors, respectively (Figure 1D and Figures 6E, 6F). Finally, in all cell types, the down-regulation of the pluripotency factors OCT4, SOX2 and NANOG was observed (Figures 1B-D), which confirmed their differentiation. [205] Twenty-seven (27) lncRNAs were screened (Table 5) that participate in regulation of gene expression (Q. Sun, Q. Hao, and K. V. Prasanth, “Nuclear Long Noncoding RNAs: Key Regulators of Gene Expression,” Trends in Genetics, vol.34, no.2, pp.142–157, Feb.2018, doi: 10.1016/j.tig.2017.11.005.), including some that are known to form condensates (T. Yamazaki et al., “Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation,” Mol. Cell, vol. 70, no. 6, pp. 1038-1053.e7, 21 2018, doi: 10.1016/j.molcel.2018.05.019). [206] Table 5: lncRNAs screened (Primer Sequences used are as listed above in Table 3)

[207] It was found that the vast majority of lncRNAs screened, 24 of the 27 screened lncRNAs, were either up- or down-regulated upon differentiation, but mostly not in an obvious differentiation stage-specific manner (Figures 1E, 1F). [208] A striking example of lineage-specific regulation was the induction of H19 (p<0.0001) in lung progenitor cells. Importantly, several lncRNAs were upregulated in all germ layers and stages including PINCR, LINC00472 and NEAT1_2 (p<0.05 in ≥5 lineages), in contrast to lncRNAs such as MALAT1, which were mostly insensitive to the lineage and stage. NEAT1_2 was chosen for an in-depth analysis of condensation behavior because it is well known to form paraspeckles that have been linked to the regulation of development and Differentiation. Example 3: Atlas of paraspeckle trajectories during cell fate conversions [209] Objective: To identify cellular features associated with the formation of paraspeckles. [210] Results: As a basis for identifying cellular features that are associated with the formation of paraspeckles, hPSCs were differentiated to more than 20 cell types and quantified foci of NEAT1_2, the facultative marker of paraspeckles, using single molecule FISH (smFISH). Mesoderm was represented by differentiating MSCs to adipocytes and osteocytes, lateral mesoderm to cardiomyocytes, and intermediate mesoderm to nephron progenitors and matured nephrons; definitive endoderm cells were differentiated to hepatocytes and lung progenitors; NSCs, which belong to ectoderm, were differentiated into motor neurons and astrocytes, and cortical neuron progenitors were cultured to a mature state; neural crest progenitors, which give rise to multiple lineages that migrate throughout the body, were produced from neurospheres (R. Bajpai et al., “CHD7 cooperates with PBAF to control multipotent neural crest formation,” Nature, vol.463, no.7283, pp.958–962, Feb.2010, doi: 10.1038/nature08733). Extraembryonic tissues were represented by trophoblast progenitors that were differentiated from hPSCs (C. Krendl et al., “GATA2/3-TFAP2A/C transcription factor network couples human pluripotent stem cell differentiation to trophectoderm with repression of pluripotency,” Proc. Natl. Acad. Sci. U.S.A., vol. 114, no. 45, pp. E9579–E9588, 07 2017, doi: 10.1073/pnas.1708341114), and myotubes, keratinocytes and fibroblasts were derived from primary tissues (Figure 1A). [211] Importantly, the cell type classifications were based on the analysis of characteristic proteins and transcripts as follows: differentiated MSCs exhibited lipid droplets and calcium deposits, which are expected in adipocytes and osteocytes, respectively (Figures 6G, 6H); differentiation of lateral mesoderm progenitors led to up-regulation of cardiomyocyte progenitor markers including NKX2.5 and ISL1 (and spontaneous beating was observed), while the early mesoderm markers T and MESP1 were down-regulated (Figure 6I); the expression of markers of the developing kidney, SIX2, PAX2 CDH5, WT1 and additional nephron progenitor markers was overtly apparent (Figure 2A and Figures 6J, 6K). In the direction of endoderm differentiation, liver markers AFP, ALB, HNF4A were strongly induced (Figure2A and Figure 6L). Characterization of the neuronal cell populations was based on the formation of TUBB3 and NFH positive axons in the case of motor neurons, MAP2 positive axons in the case of cortical neurons, and GFAP positive star-like projections in the case of astrocytes (Figure 2A). Moreover, these cell populations expressed the characteristic transcription factors MNX1, ISL1, TBR1 and SOX9, respectively (Figure 2A), which were confirmed by analysis of gene expression together with neuronal markers CHAT and TBR2 as well as markers of astrocytes SLC1A2 and SLC1A3 (Figures 6M-6O). Finally, the identity of fibroblasts and keratinocytes was validated by expression of VIM / HSP47 and KRT14 / IVL, respectively (Figure 2A). [212] Inspection of the cell atlas confirmed the previous observations that the number of paraspeckles increases when hPSCs exit the pluripotent state (M. Modic et al., “Cross-Regulation between TDP-43 and Paraspeckles Promotes Pluripotency-Differentiation Transition,” Mol. Cell, vol.74, no.5, pp.951-965.e13, Jun.2019, doi: 10.1016/j.molcel.2019.03.041; L.-L. Chen and G. G. Carmichael, “Altered nuclear retention of mRNAs containing inverted repeats in human embryonic stem cells: functional role of a nuclear noncoding RNA,” Mol. Cell, vol.35, no.4, pp. 467–478, Aug. 2009, doi: 10.1016/j.molcel.2009.06.027). Moreover, it was apparent that the increase in the number of paraspeckles during exit from pluripotency is a general phenomenon that encompassed progenitors of the three germ layers, neural crest progenitors as well as extraembryonic trophoblast progenitors (Figure 2B and Figures 7A, 7C). [213] Because these types of progenitors exhibited vastly different transcriptional programs and epigenetic landscapes, these results indicated that the regulation of paraspeckle formation is connected to a general mechanism that regulates the nucleus. Formation of heterochromatin upon differentiation is one such mechanism, however, it was not deemed likely that heterochromatin was involved in the mechanism that drives paraspeckle formation, because at later stages of differentiation, the number of paraspeckles varied considerably between related types of cells. For instance, differentiated cell types that belong to the mesoderm lineage displayed either 2.6 - 5.7 paraspeckles per cell on average, or 13.8 - 26 in MSCs and their adipocyte and osteocyte progeny (Figure 2B and Figures 7A-7C). Similarly, in the neural lineages, there was a striking difference between the number of paraspeckles in the neurons and astrocytes that were derived from NSCs (Figures 2B, 2C and Figure 7C). Moreover, hepatocytes and lung progenitors exhibited differences in the number of paraspeckles, albeit having a common endoderm progenitor. Additional evidence indicating that the regulation of the number of paraspeckles is not overtly determined by cell lineages or timing of differentiation were a) the weak correlation between the number of paraspeckles and the time point of differentiation (Figure 7D), b) the oscillations in the number of paraspeckles during cellular reprogramming (the reverse process of differentiation) (Figure 2B and Figures 7H-7J) and c) that adult dermal fibroblasts exhibited significantly more paraspeckles compared to newborn foreskin fibroblasts (Figure 2B and Figure 7C). More evidence that paraspeckle amount represents a cell-intrinsic property stem from the fact that increased passaging of neural stem cells did not change the number of paraspeckles (Figure 7D) and that primary human astrocytes exhibited similar amount of paraspeckles as in vitro differentiated astrocytes (Figure 2D). [214] To further analyze cellular parameters that could influence paraspeckle formation, it was asked whether similar amounts of paraspeckles appear in equivalent types of cells in the mouse. Strikingly, it was found that despite the trends being similar, i.e. astrocytes exhibiting greater amounts of paraspeckles compared to cardiomyocytes, hepatocytes and ESCs, the number of paraspeckles in the respective types of cells in the mouse was significantly lower (Figure 2D). These results were substantiated by showing that the general correlation between the signal intensity of smFISH and the number of paraspeckles counted in human and mouse cells was very high, and that the level of NEAT1_2 transcript was generally correlated (Figures 7F, 7G). [215] Conclusion: Altogether, it was concluded that cellular differentiation creates diverse patterns of paraspeckle kinetics, which are not overtly correlated with developmental lineages or timing. Example 4: Paraspeckle amount correlates with the size of the nucleus [216] One parameter of the nucleus that varies drastically between different cell types is its size. Therefore, the cell atlas image database was used to ask whether size scaling of the nucleus can explain the different amounts of paraspeckles in different cell types. Strikingly, positive correlations between the number of paraspeckles and the size of nuclei were noticed when inspecting individual fibroblasts (Figures 3A, 3B). Moreover, a greater amount of paraspeckles was noted in fibroblasts that were derived from the adult compared with newborn foreskin fibroblasts (Figure 3B and Fig 7C), which could be the result of up-regulation in cellular senescence that is accompanied with nuclei size increase. These results prompted investigation into whether the size of the nucleus is in general predictive for paraspeckle quantity in different types of cells (Figure 2). Strikingly, analyzing nuclei size in all the cell types of the atlas revealed a correlation with the number of paraspeckles (Figure 3C). Furthermore, it was found that the oscillating pattern of paraspeckle formation during reprogramming could be explained by changes in the average nucleus size during the process (Figure 3D). This led us to hypothesize that the differences in paraspeckle amount between human and mouse astrocytes and MSCs (Figure 2D) are due to nucleus size differences. Indeed, adjusting the number of paraspeckles in accordance to nucleus size differences between human and mouse MSCs and astrocytes showed that the normalized values of paraspeckles are similar between the species (Figures 3E, 3F). Finally, the differences in paraspeckles numbers between human newborn and adult fibroblasts could be explained in the same way by nucleus size changes (Figures 3G, 3H). These results provided a first explanation for the high degree of variability in the number of paraspeckles observed between cells of the same type, between different types of cells and between species. [217] Next, to assess whether the size of the nucleus determines the amount of paraspeckles or vice versa, NEAT1-/- and NEAT1ΔpA hESCs were analyzed, which were either devoid of paraspeckles or exhibited 2-fold increase in the amount of paraspeckles due to the deletion of the internal polyA site (Figure 3I). Analyzing the size of nuclei did not reveal differences between NEAT1-modified cell lines compared to wildtype (Figure 3J). [218] Conclusion: It appears to be the nucleus size that determines the amount of paraspeckles. Example 5: DNA accessibility is required for paraspeckle assembly [219] Objective: The broad range in the number of paraspeckles in cells with different size of nuclei led to interrogation of what common traits could regulate their structural similarity across different types of cells. [220] Results: Because several long non-coding RNAs (lncRNAs) including NEAT1_2 and MALAT1 have been associated with formation of RNA-dsDNA triple helix structures through base pairing in the major groove, it was hypothesized that conformational changes of the DNA helix could perturb paraspeckles. It was therefore tested, whether small molecules such as ActD that bind the dsDNA can promote the disassembly of paraspeckles. Strikingly, the appearance of numerous small NEAT1_2 speckles were noted that peaked between 1 and 2 hours in diverse types of cells that were treated by ActD, including in trophoblast progenitors, NSCs, and definitive endoderm progenitors that were derived from hPSCs, as well as in primary astrocytes and adult dermal fibroblasts (Figure 4A and Figure 8A). [221] Importantly, the numbers of the small NEAT1_2 speckles matched the number of paraspeckles observed in the respective cell types (Figures 2B, 4C), indicating that ActD induced the disintegration of paraspeckles. Contrarily, it was noted that core paraspeckle proteins, namely SFPQ and NONO localized to perinucleolar caps after addition of ActD (Figure 8B) which is in line with previous observations that reported perinucleolar localization of paraspeckle proteins after transcriptional inhibition and during cell division when NEAT1_2 is down-regulated. This indicated that the small speckles of NEAT1_2 arising upon ActD treatment are not functional. [222] Based on these findings, the effects of Hoechst 33342 and Mithramycin A, which induce conformational changes of the DNA helix by binding to the minor groove, were also tested. These molecules led to the appearance of small NEAT1_2 speckles that exhibited similar patterns of accumulation and decay as after treatment by ActD (Figures 4B, 4D). Importantly, α-Amanitin (selective inhibitor of RNA polymerases II, III and IV) did not induce immediate paraspeckle disintegration (Figures 4B, 4D), which ruled out the possibility that inhibition of RNA polymerases was the underlying cause. Nevertheless, the disappearance of NEAT1_2 following several hours of continuous treatment was likely due to other mechanisms that interfere with transcription, and it has been shown before that inhibition of transcription impairs paraspeckle formation. [223] It is known that some small DNA-binding molecules can induce double-strand breaks, which can be analyzed by the appearance of γ-H2A.X foci. This was found to be the case following ActD treatment but not following Hoechst or Mithramycin A treatment (Figure 4E and Figure 8C). [224] Because ActD and Mithramycin A are used in chemotherapy protocols to treat several types of cancer, it was of interest to know whether paraspeckle disintegration could be induced by other chemotherapeutic reagents. This was tested by treating the cells with the microtubule inhibitor Vincristine, the topoisomerase II inhibitor Etoposide, or with Flavopiridol, an inhibitor for cyclin-dependent kinases. [225] A significant increase in small NEAT1_2 speckles were observed after treatment by Etoposide and Flavopiridol, but not by Vincristine (Figure 4F), and since only the first two molecules were shown to bind dsDNA, this supported our conclusion that DNA binding by small molecules induces paraspeckle disintegration (Figure 8D). [226] Finally, to test whether small DNA-binding molecules can in general disintegrate lncRNA condensates, MALAT1 speckles were analyzed by smFISH after ActD treatment. Strikingly, it was found that MALAT1 speckles disintegrate with similar kinetics as paraspeckles (Figures 8E, 8F). [227] Conclusions: Paraspeckle disintegration is not mediated by DNA damage or inhibition of RNA polymerases, and DNA helix binding serves as structural basis for assembly and maintenance of paraspeckles and other nuclear lncRNA condensates. Example 6: NEAT1_2 regulates differentiation [228] Objective: The results revealed that paraspeckles are dynamically regulated in cellular differentiation by the size of the nucleus and DNA accessibility. The next step was to analyze their functional role during the differentiation of germ layer progenitors. [229] Results: In order to analyze their functional role during the differentiation of germ layer progenitors, which commonly up-regulate paraspeckles upon exit from pluripotency (Figure 2), a series of genetically edited lines were created. Specifically, the promoter, the transcription start site, and downstream sequences of NEAT1 were deleted in one line, and in another, the triple helix (TH) sequence that resides in the 3`end of the gene, which is required for processing of NEAT1_2 was deleted, and therefore it was hypothesized that it will produce a knock-down phenotype. Accordingly, paraspeckles and expression of NEAT1_2 in the NEAT1-/- line were not observed, and 57% less paraspeckles were observed in the NEAT1ΔTH line after spontaneous differentiation (Figures 5A-D). [230] By analyzing the expression of developmental markers, it was found that the pluripotency characteristics in undifferentiated NEAT1-/- and NEAT1ΔTH cells were intact with exception of premature up-regulation of FOXA2 and PAX6 (Figure 9A). Remarkably, the induction of spontaneous differentiation accelerated the down-regulation of pluripotency transcription factors OCT4 and NANOG, and cell surface markers TRA1-60 and SSEA5 in NEAT1-/- and NEAT1ΔTH cells compared to the parental cell line, one day after the time when paraspeckles form during spontaneous differentiation (Figures 5E-5G and Figures 9B, 9C). A similar acceleration was observed during neuroectoderm differentiation, albeit the gene expression patterns became similar to the parental line at later stages of the differentiation protocol (Figures 5H, 5I and Figure 9D). As different phenotypes for the NEAT1-/- and NEAT1ΔTH human cell lines were not observed (Figures 5E-I and Figure 9A-9D), although the latter produced the short isoform (Figure 5D), it was hypothesized that NEAT1_1 is dispensable for the differentiation of germ layer progenitors. Indeed, analyzing the differentiation of a hPSC line that harbored a deletion of the internal polyadenylation site in NEAT1 (NEAT1ΔpA) and hence was not capable to express NEAT1_1, did not reveal a difference in the up-and down-regulation of differentiation and pluripotency genes (Figures 9E-9G). [231] To validate these findings, another knock-out strategy was employed, by inserting a polyA stop cassette approximately 1500 base pairs downstream of the NEAT1 transcription start site, thereby generating a cell line that expressed only a truncated version of NEAT1_1 but no NEAT1_2 (Figures 5B-D). [232] As observed with the NEAT1-/- and NEAT1ΔTH lines, NEAT1STOP cells exhibited down- regulation of the pluripotency transcription factors OCT4/NANOG and the surface markers SSEA4/SSEA5/TRA1-60 during spontaneous differentiation (Figures 9H-9K). [233] Conclusion: Only the condensate form of NEAT1 lncRNA, namely paraspeckles, is functionally important during spontaneous or neural differentiation of hPSCs by slowing down the process, but cells can compensate the loss of paraspeckles when treated by differentiation stimuli for an extended period of time. Example 7: Summary of Findings from Examples 2-6 [234] LncRNAs are predominantly localized in the nucleus where some have been implicated in the architectural organization of chromatin by formation of condensates. In this regard, NEAT1 is paradigmatic for studying lncRNA condensation because it is the vital scaffold for the formation of paraspeckles together with several RNA binding proteins that have been well-characterized. Despite major advancements in understanding the molecular structure of paraspeckles and the regulation of NEAT1 RNA, basic questions pertaining to the regulation of paraspeckle formation, amounts in cells, and their molecular and cellular functions remain open. Here, several observations are made that shine light on these questions. [235] First, it was found that the amount of paraspeckles in a given cell within a population, or among different cell populations, is generally scaled according to the size of the nucleus. This finding potentially has important implications; for example, it could indicate that paraspeckles are engaged in feedback(s) that slow-down cellular processes when nuclei reach set size(s), such as energy production. In this regard, paraspeckles have been implicated recently in the regulation of mitochondria homeostasis, together with their up-regulation during pathogen infection, and in cancer, the latter often accompanied by changes in nuclear morphology. Here it was found that hPSCs that lack paraspeckles are poised to retain pluripotency upon differentiation, which could be connected to the control of biochemical pathways. Interestingly, it was noted that certain cell types greatly deviate from the nucleus size rule, most notably hepatocytes, which could indicate complex forms of regulation by paraspeckles in specific types of cells. The nucleus sizing effect could also indicate that the regulation of paraspeckles is more pronounced in human stem cell differentiation, and plausibly also in human development, compared to the equivalent processes in the mouse, because as was shown here, nuclei in the mouse are often significantly smaller and contain fewer paraspeckles. In line with this idea, paraspeckles are not vital for mouse development past the blastocyst stage, although their knock-down in embryos at the gastrulation stage increases the odds of developmental perturbations. Collectively, the new questions about nuclei scaling and its connection to paraspeckle-mediated regulation emphasize that dissecting the molecular and cellular functions of paraspeckles should take into account processes that could be affected by nuclear scaling. [236] Second, by applying small molecules that can associate with the DNA, strong evidence was found that paraspeckles and splicing speckles are tethered to the DNA, most likely by forming triple helix structures. The fact that molecules with vastly different structures similarly promoted paraspeckle disintegration, indicates that conformational changes of DNA are the root cause. [237] These findings imply that numerous species of lncRNA condensates could be tethered to the genome at any given moment and regulate its biochemical functions. If this is indeed the case, it is plausible that aberrant regulation of tethered lncRNA condensates could be involved in human disease. In line with this prediction, a growing list of lncRNAs has been associated with diverse forms of disease pathogenesis, including diabetes and cancer. Therefore, the identification here of small molecules that disintegrate tethered lncRNA condensates indicates a potential novel therapeutic approach that is based on lncRNA disintegration. [238] The fact that several of the molecules that are implicated here in disintegration of paraspeckles are FDA approved chemotherapies, suggests that their clinical assessments could be expedited. On the other hand, the realization that chemotherapies that bind DNA can promote disintegration of lncRNA condensates raises the possibility that on-target and/or side effects in cancer therapy are mediated by changes of lncRNA functions. Therefore, our results create a new path to understand the mode-of-action in the treatment of certain cancers, for example, Actinomycin D, Etoposide, and Mithramycin A are commonly used chemotherapies in the treatment of osteosarcoma. [239] Taken together with our assessment of the cellular functions of paraspeckles, indicating their importance for slowing down differentiation processes, these results suggest that DNA helix tethering of paraspeckles is important for developmental regulation. [240] Conclusion: Figure 10 provides a summary of the findings described in Examples 2-7. Briefly, the functions of chromatin-embedded granules, such as paraspeckles, are poorly characterized, and their intracellular and intercellular patterns seem random. By creating an atlas of differentiated cell types as a resource to study lncRNAs and paraspeckles, it was discover that the nucleus size scaling governs the formation of paraspeckles. Moreover, the first small molecule compounds were identified that disintegrate paraspeckles and lncRNA condensates that are tethered to the genome. It was shown that these mechanisms are crucial for stem cell differentiation. This indicates that regulation of lncRNAs in neurodegeneration, cancer and cellular differentiation is associated to nuclear size scaling. [241] While certain features of the lncRNAs and the use of small molecules to disintegrate condensates comprising lncRNAs have been illustrated and described herein, many modifications, substitutions, changes, and equivalents will now occur to those of ordinary skill in the art. It is, therefore, to be understood that the appended claims are intended to cover all such modifications and changes as fall within the true spirit of the disclosure herein.

Claims

CLAIMS What is claimed is: 1. A composition comprising a small molecule that binds to double stranded DNA (dsDNA) and disintegrates or disrupts lncRNA condensates of a lncRNA-dsDNA complex, for use treating a human disease or condition associated with long non-coding RNA (lncRNA) condensates.

2. The composition for use of claim 1, wherein said binding comprises minor groove binding of said dsDNA, both major and minor groove binding of said dsDNA, or intercalating within said dsDNA.

3. The composition for use of any of claims 1 and 2, wherein said binding comprises (a) non-sequence specific binding; (b) structural specific binding; (c) binding that does not inhibit RNA transcription; or (d) binding that introduces a double strand break in the DNA; or (e) any combination thereof.

4. The composition for use of any of claims 1-3, wherein said lncRNA condensate comprises a paraspeckle.

5. The composition for use of any of claims 1-4, wherein said binding disintegrates or disrupts or a combination thereof, a lncRNA condensate.

6. The composition for use of any of claims 1-5, wherein said lncRNA is selected from the group consisting of PVT1, KCNQ1OT1, AIRN, PINT, Linc-Pint, MALAT1, TERC, MEG3, LINC00472, TUG1, KLRA1P, PINCR, MANTIS, LncPRESS1, HAND2-AS, HOTAIR, HOTTIP, Braveheart, Fendrr, ANRIL, Chaer, pRNA, Dum, PAPAS, Xist, Air, Dali, LincRNA-p21, CCND-Nat, MIAT, ecCEBPA, RMRP, PANDA, H19, TARID, SLERT, FIRRE, ANRASSF1, PARTICLE, APTR, NEAT1_2, or any combination thereof.

7. The composition for use of any of claims 1-6, wherein said small molecule comprises a chemotherapeutic agent.

8. The composition for use of any of claims 1-6, wherein said small molecule comprises an anthracycline drug.

9. The composition for use of any of claims 1-8, wherein said small molecule comprises Actinomycin D (ActD), Doxorubicin, Mithramycin A, Mitomycin, Mitoxantrone, Etoposide, or Flavopriridol.

10. The composition for use of any of claims 1-9, wherein said human disease or condition comprises a cancer, a neurological disease, an autoimmune disease, or a cardiac disease or condition.

11. The composition for use of claim 10, wherein said cancer comprises Wilms' tumor, a childhood rhabdomyosarcoma, a Ewing's sarcoma or metastatic growth thereof, comprises a lymphoma, a non-lymphocytic leukemia, small cell lung cancer, or a glioblastoma multiforme, refractory testicular tumors, non-seminomatous testicular cancer, testicular cancer, hypercalcemia and hypercalciuria associated with an advanced form of a cancer a lymphoblastic leukemia, an acute myeloblastic leukemia, a Wilms’ tumor, neuroblastoma, a soft tissue and bone sarcoma, a breast carcinoma, an ovarian carcinoma, a transitional cell bladder carcinoma, a thyroid carcinoma, a gastric carcinoma, a Hodgkin’s disease, a malignant lymphoma or a bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types, an esophageal cancer, a leukemia (lymphoid), a lung cancer, a liver cancer, axillary lymph node involvement following resection of primary breast cancer, or a malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, or urinary bladder 12. The composition for use of claim 10, wherein the small molecule is ActD and said cancer comprises a Wilms' tumor, a childhood rhabdomyosarcoma, a Ewing's sarcoma or metastatic growth thereof, or a non-seminomatous testicular cancer. 13. The composition for use of claim 11, wherein said treating comprises a part of a combination chemotherapy and/or multi-modality treatment regimen. 14. The composition for use of claim 10, wherein said small molecule is Doxorubicin and said cancer comprises a lymphoblastic leukemia, an acute myeloblastic leukemia, a Wilms’ tumor, neuroblastoma, a soft tissue and bone sarcoma, a breast carcinoma, a primary breast cancer, an ovarian carcinoma, a transitional cell bladder carcinoma, a thyroid carcinoma, a gastric carcinoma, a Hodgkin’s disease, a malignant lymphoma, or a bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types. 15. The composition for use of claim 14, wherein when said subject is female and said cancer comprises axillary lymph node involvement following resection of primary breast cancer, said treating comprises an adjuvant therapy. 16. The composition for use of claim 10, wherein said small molecule is Mithramycin A and said cancer comprises testicular cancer, or hypercalcemia and hypercalciuria associated with an advanced form of a cancer. 17. The composition for use of claim 10, wherein said small molecule is Mitomycin and said cancer comprises a malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, or urinary bladder. 18. The composition for use of claim 10, wherein said small molecule is Etoposide and said cancer comprises a lymphoma, a non-lymphocytic leukemia, a small cell lung cancer, or a glioblastoma multiform, or said use is in combination with other chemotherapeutic agents and said cancer comprises refractory testicular tumors. 19. The composition for use of claim 10, wherein said small molecule is Flavorpiridol and said cancer comprises an esophageal cancer, a leukemia (lymphoid), a lung cancer, a liver cancer, or a lymphoma. 20. The composition for use of claim 10, wherein said neurological disease or condition comprises schizophrenia, bipolar disorder, cerebral ischemia, frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple system atrophy, spinal muscular atrophy, multiple sclerosis, Cerebral Palsy, Autism Spectrum Disorder, Epilepsy, secondary (chronic) progressive multiple sclerosis, a progressive relapsing multiple sclerosis, or a worsening relapsing- remitting multiple sclerosis or Huntington’s disease. 21. The composition for use of claim 10, wherein said small molecule is Mitoxantrone and said neurological disease comprises secondary (chronic) progressive multiple sclerosis, a progressive relapsing multiple sclerosis, or a worsening relapsing- remitting multiple sclerosis. 22. The composition for use of claim 10, wherein said autoimmune disease comprises diabetes. 23. An in vitro method of identifying a treatment agent for a human subject suffering from a disease or condition associated with a long non-coding RNA (lncRNA) condensate, said method comprising (a) collecting a biological sample comprising cells from the subject suffering from said disease or conditions associated with a lncRNA condensate; (b) culturing a portion of said cells of said biological sample with a small molecule that binds to double stranded DNA (dsDNA) and culturing a control portion of said cells without said small molecule; (c) incubating said cultures under physiological conditions for a period of time; (d) measuring the number and size of lncRNA condensates present in the portion of cells incubated with said small molecule and in the control portion of cells; and (e) comparing the number and size of the lncRNA condensates present in both portions, and determining if the number or size or both of said lncRNA condensates is reduced in the portion incubated with the small molecule; wherein if the number or size or both of said lncRNA condensates is reduced in the portion incubated with the small molecule compared with the control portion, then the small molecule is identified as a treatment agent for said subject. 24. The method of claim 23, wherein said lncRNA condensate comprises a paraspeckle. 25. The method of any of claims 23-24, wherein said biological sample comprises urine, blood, a tissue biopsy, or a tumor tissue biopsy. 26. The method of any of claims 23-25, wherein said cells comprise an intact nucleus. 27. The method of any of claims 23-26, wherein said cells comprise peripheral blood mononuclear cells (PBMC), adult fibroblasts, neonatal fibroblasts, neural crest cells, mesenchymal stem cells, adipocytes, myotubes, nephron progenitor cells, nephrons, osteocytes, cardiomyocytes, lung progenitor cells, hepatocytes, neural stem cells, motor neurons, astrocytes, cortical neuron progenitor cells, cortical neurons, neural stem cells, keratinocytes, trophoblast progenitor cells, endoderm cells, mesoderm cells, or any combination thereof. 28. The method of any of claims 23-27, wherein said binding comprises minor groove binding of said dsDNA, both major and minor groove binding of said dsDNA, or intercalating within said dsDNA. 29. The method of any of claims 23-28, wherein said binding comprises (a) non-sequence specific binding; (b) structural specific binding; (c) binding that does not inhibit RNA transcription; or (d) binding that introduces a double strand break in the DNA; or (e) any combination thereof. 30. The method of any of claims 23-29, wherein said incubation comprises incubating for about 1 to 30 days. 31. The method of any of claims 23-30, wherein said binding disintegrates or disrupts or a combination thereof, a lncRNA condensate. 32. The method of any of claims 23-31, wherein said lncRNA is selected from the group consisting of PVT1, KCNQ1OT1, AIRN, PINT, Linc-Pint, MALAT1, TERC, MEG3, LINC00472, TUG1, KLRA1P, PINCR, MANTIS, LncPRESS1, HAND2-AS, HOTAIR, HOTTIP, Braveheart, Fendrr, ANRIL, Chaer, pRNA, Dum, PAPAS, Xist, Air, Dali, LincRNA-p21, CCND-Nat, MIAT, ecCEBPA, RMRP, PANDA, H19, TARID, SLERT, FIRRE, ANRASSF1, PARTICLE, APTR, NEAT1_2, or any combination thereof. 33. The method of any of claims 23-32, wherein said treatment agent identified comprises a chemotherapeutic agent. 34. The method of any of claims 23-32, wherein said treatment agent identified comprises an anthracycline drug. 35. The method of any of claims 23-32, wherein said treatment agent identified comprises Actinomycin D (ActD), Doxorubicin, Mithramycin A, Mitomycin, Mitoxantrone, Etoposide, or Flavopriridol. 36. The method of any of claims 23-35, wherein said human disease or condition comprises cancer, a neurological disease, an autoimmune disease, or a cardiac disease or condition. 37. The method of claim 36, wherein said cancer comprises Wilms' tumor, a childhood rhabdomyosarcoma, a Ewing's sarcoma or metastatic growth thereof, comprises a lymphoma, a non-lymphocytic leukemia, small cell lung cancer, or a glioblastoma multiforme, refractory testicular tumors, non-seminomatous testicular cancer, testicular cancer, hypercalcemia and hypercalciuria associated with an advanced form of a cancer a lymphoblastic leukemia, an acute myeloblastic leukemia, a Wilms’ tumor, neuroblastoma, a soft tissue and bone sarcoma, a breast carcinoma, an ovarian carcinoma, a transitional cell bladder carcinoma, a thyroid carcinoma, a gastric carcinoma, a Hodgkin’s disease, a malignant lymphoma or a bronchogenic carcinoma in which the small cell histologic type is the most responsive compared to other cell types, an esophageal cancer, a leukemia (lymphoid), a lung cancer, a liver cancer, axillary lymph node involvement following resection of primary breast cancer, or a malignant neoplasm of lip, oral cavity, pharynx, digestive organs, peritoneum, female breast, or urinary bladder 38. The method of claim 36, wherein said neurological disease or condition comprises schizophrenia, bipolar disorder, cerebral ischemia, frontotemporal dementia, Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, multiple system atrophy, spinal muscular atrophy, multiple sclerosis, Cerebral Palsy, Autism Spectrum Disorder, Epilepsy, or Huntington’s disease. 39. The method of claim 36, wherein said autoimmune disease comprises diabetes. 40. The method of any of claims 23-39, wherein when said method identifies a small molecule as a treatment agent for said subject, said method comprises a further use step (f) comprising use of a composition comprising the identified small molecule treatment agent for treating a human disease. 41. The method of claim 40, wherein said human disease or condition comprises a cancer and said small molecule identified comprises ActD, Doxorubicin, Mithramycin A, Mitomycin, Etoposide, Mitoxantrone, or Flavorpiridol, or a combination thereof.