Sculpting multi-lineage tissues

Abstract

Provided herein are, inter alia, are compositions and methods for use in sculpting multi-lineage tissues (e.g. teratomas). Provided herein are, inter alia, nucleic acid compositions and cellular compositions including sequences encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence. Also provided herein are, inter alia, methods for forming masses of cells. Further provided herein are, inter alia, method for producing cells of a desired developmental or differentiation lineage.

Description

PATENT Atorney Docket No. 048537-663001 WOSCULPTING MULTI-LINEAGE TISSUESRELATED APPLICATION DATA

[0001] This application claims the benefit of priority under 35 U. S. C. § 119(e) of U. S. Patent Application No. 63 / 729,898, filed on December 9, 2024, which is hereby incorporated by reference in its entirety' and for all purposes.SEQUENCE LISTING

[0002] The material in the accompanying Sequence Listing is hereby incorporated by reference in its entirety7. The accompanying file, named “048537-663001WO_SL_ST26.xml” was created on December 9, 2025, and is 104,087 bytes in size.GOVERNMENT SUPPORT CLAUSE

[0003] This invention was made with government support under HG012351 and OD032742 awarded by the National Institutes of Health, and under W81XWH-22- 1-0401 awarded by the Defense Health Agency, Medical Research and Development Branch. The government has certain rights in the invention.BACKGROUND

[0004] hPSCs have been used to model human developmental processes for the past two decades, and there has been significant progress made in understanding early-stage development using 2D monolayer culture systems. However, development occurs in 3 dimensions, and thus better model systems have since been developed to recapitulate key developmental phenomena in 3D 4. Organoids have played a major role in this transition to 3 dimensions, as they have been used to make complex organ mimics that faithfully recapitulate the cell-type composition, cytoarchitecture and functions of their in vivo counterparts. Organoids have been used to generate a diverse array of lineage-specific model systems, however they suffer in that the extrinsic media conditions can typically only dictate the tissue towards one particular lineage at a time. This is in contrast to how organogenesis occurs in utero. as it has been extensively studied that neighboring lineages in the developing embryo can guide the proper differentiation and maturation of many organ systems through paracrine and mechanical signaling. Thus, a tissue engineering platform in which all germ lay ers can differentiate simultaneously is ideal to allow for any cross-germ layer interactions that are necessary for proper organ development. Providedherein, inter alia, are compositions and methods of use thereof to address these and other problems in the art.BRIEF SUMMARY

[0005] In an aspect is provided a nucleic acid including a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein includes a compound-inducible dimerizing domain and an apoptotic domain.

[0006] In another aspect is provided a recombinant cell including the nucleic acid provided herein including embodiments thereof.

[0007] In another aspect is provided a mass of recombinant cells, wherein each cell within the mass of recombinant cells includes a nucleic acid including a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein includes a compound-inducible dimerizing domain and an apoptotic domain.

[0008] In an aspect is provided an organism including the mass of recombinant cells provided herein including embodiments thereof, wherein the organism is a non-human organism.

[0009] In another aspect is provided a method of forming a mass of recombinant cells, the method includes administering to a subject a plurality of recombinant pluripotent stem cells and allowing the plurality of recombinant pluripotent stem cells to divide for a first period of time, thereby forming the mass of recombinant cells, wherein each recombinant pluripotent stem cell in the plurality of recombinant pluripotent stem cells includes a nucleic acid including a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein includes a compound-inducible dimerizing domain and an apoptotic domain.

[0010] In another aspect is provided a method for inducing apoptosis in a first portion of recombinant cells in a mass of recombinant cells, the method includes: (a) culturing a mass of recombinant cells in vitro for a first period of time, (b) contacting the mass of recombinant cells with a compound; and (b) culturing the mass of recombinant cells for a second period of time in the presence of the compound, wherein each recombinant stem cell in the mass of recombinant cells includes a nucleic acid including a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducibledimerizing apoptotic protein includes a compound-inducible dimerizing domain and an apoptotic domain wherein the mass of recombinant cells includes a first portion of recombinant cells and a second portion of recombinant cells, wherein the second portion of recombinant cells express a miRNA, thereby blocking translation of the inducible dimerizing apoptotic protein, and allowing the second portion of recombinant cells to divide within the second period of time, wherein the first portion of recombinant cells does not express the miRNA, thereby inducing apoptosis in the first portion of recombinant cells in the mass of recombinant cells.

[0011] In another aspect is provided an isolated nucleic acid including a dimerizing domain, an inducible apoptotic domain, and a lineage-specific binding domain.

[0012] In another aspect is provided an expression vector including the isolated nucleic acid provided herein including embodiments thereof.

[0013] In another aspect is provided a cell including the isolated nucleic acid provided herein including embodiments thereof or the expression vector provided herein including embodiments thereof.

[0014] In another aspect is provided a method for generating a multi-lineage population of cells, the method including: (a) contacting a population of cells with one or more of the isolated nucleic acids provided herein including embodiments thereof or the expression vector provided herein including embodiments thereof; (b)allow the cells to express the one or more isolated nucleic acids; and (c) contacting the population of cells with a chemical dimerizer, wherein the chemical dimerizer induces the dimerization of one or more dimerizing domains.BRIEF DESCRIPTION OF THE DRAWINGS

[0015] FIGS. 1A-1B show attB Recombination Mechanism. FIG. 1A: Schematic showing the Bxbl-mediated recombination event, following introduction of Bxbl recombinase and an attB donor plasmid. FIG. IB: Gel electrophoresis depicting the attR and attL recombination site amplicons of the after BXB1 -mediated recombination into the AAVS 1 locus.

[0016] FIGS. 2A-2C show miRNA-mediated Inducible Caspase9 Construct Mechanism. FIG.2A: microRNA-mediated inducible Caspase9 gene circuit. FIGS. 2B-2C: Schematic showing the function of the microRNA-mediated Caspase9 circuit with (FIG. 2B) and without (FIG. 2C) an endogenous lineage-specific microRNA-RISC complex.

[0017] FIGS. 3A-3B show iCaspase-mirEmpty Kill Curve. FIG.3A: Schematic of the iCaspase9-mirEmpty gene construct integrated into the AAVS1 locus of attp-mCheny cells after BXBl-mediated recombination. FIG. 3B: Assessing cell viability after 24 and 48 hours of AP20187 exposure to iCaspase-mirEmpty cells.

[0018] FIGS. 4A-4D show mir302b-mediated GFP Silencing in Ell ESCs. The functionality of lineage-specific miRNA-mediated gene circuit silencing, in which a pluripotency miRNA -mir302b - target site is inserted in the 3’ UTR of GFP was assessed. This is compared to a negative control, GFP-mirEmpty, in which there is no micoRNA target site in the 3’ UTR of GFP. FIGS. 4A-4B: FACS plots for Hl ESCs transduced with lentivirus encoding for GFP-mirEmpty (FIG. 4A) and GFP-mir302b (FIG.4B). FIGS. 4C-4D: FACS plots for 293Ts transduced with lentivirus encoding for GFP-mirEmpty (FIG. 4C) and GFP-mir302b (FIG. 4D).

[0019] FIGS. 5A-5D show' mir9-mediated iCaspase9 Silencing in Hl -derived Neurons. The functionality of lineage-specific miRNA-mediated gene circuit silencing, in w hich a neural miRNA - mir9 - target site is inserted in the 3‘ UTR of iCaspase-GFP w as assessed. This target site is inserted once (lx) or 4 times in tandem (4x). These are compared to a negative control, GFP-mirEmpty, in which there is no micoRNA target site in the 3’ UTR of iCaspase-GFP. FIG.5A: FACS plots for iCaspase-GFP-mirEmpty neurons. FIG. 5B: FACS plots for iCaspase-GFP -mir9Target-lx neurons. FIG. 5C: FACS plots for iCaspase-GFP-mir9Target-4x neurons. FIG.5D: CCK8 viability’ of neurons after one day of iCaspase induction via 10 nm of AP20187.

[0020] FIGS. 6A-6C show mir9-mediated Neural Enrichment in Teratomas. FIG. 6A: Growth curves for -AP20187 teratomas (n=4). FIG.6B: Growth curves for +AP20187 teratomas (n=4).FIG. 6C: Representative H& E stains from -AP20187 (left) and +AP20187 (right) teratomas.

[0021] FIGS. 7A-7I show' engineering of micro RNA mediated suicide circuit cell lines and in vitro validation of functionality. FIG. 7A: miRNA-mediated inducible Caspase9 gene circuit, schematic showing the function of the microRNA-mediated Caspase9 circuit without (top panel) and with (bottom) an endogenous lineage specific microRNA-RISC complex. FIG. 7B:Schematic showing the targeting of the genomic AAVS1 locus in ESCs via electroporation of Cas9, gRNA, and a AAVS1 donor plasmid. These cells are single cell cloned, and then genotyped to check for proper transgene insertion. FIG. 7C: Gel electrophoresis depicting the left and right arm amplicons of the AAVS1 integrated transgene. FIG. 7D: Schematic showing the Bxbl -mediated recombination event, following introduction of Bxbl recombinase and an attB donor plasmid. FIG. 7E: Gel electrophoresis depicting the attR and attL recombination siteamplicons of post BXB1 -mediated recombination into the AAVS1 locus for representative cell line with miRNA9 Target sites. FIG. 7F: Schematic demonstrating experiment where miRNA-regulated suicide circuit was incorporated into a cell. Three constructs were used: iCaspase9-GFP-mir 9 Target-lx (mir9Target-lx) with one target site in the 3' UTR; iCaspase9-GFP-mir 9 Target-4x (mir9Target-4x) with four target sites; and iCaspase9-GFP-mirEmpty (mirEmpty) which was a control lacking target sites. FIG. 7G: Quantification of EGFP and mCherry expression via flow cytometry at day 7. FIG. 7H: Quantification of fold change in mRNA expression of MAP2 (left panel) and TUBB3 (right panel) in day 7 neurons compared to undifferentiated cells. FIG. 71: Viability of cells expressing the mirEmpty, mir9Target-lx (mir9_lx), mir9Target-4x (mir9_4x) after addition of 1 pM AP20187 for 24 h. Neurons expressing mir9Target-4x were significantly more viable than either mirEmpty- or mir9Target-Ix-expressing neurons.

[0022] FIGS. 8A-8G show miRNA 9 based suicide circuit enables enrichment of neural lineage in-vivo. FIG. 8A: Schematic depicting experimental workflow for neural lineage enrichment in miR9Target_4x teratomas. FIG. 8B: Hematoxylin and Eosin stain of representative AP20187 untreated and treated mir9Target_4x teratomas. FIG. 8C:Immunofluorescence stains from representative AP20187 untreated and treated mir9Target_4x teratomas for mature neuron marker MAP2 and post mitotic neural marker neuron-specific 03-tubulin (TuJl), counter stained with DAPI. FIG. 8D: Percent of cells that are Neurons (MAP2+ and / or TuJl+) or not Neurons (Map2- and TuJl-) as determined by fluorescence intensity thresholding of Immunofluorescence stains of teratoma sections. FIG. 8E: Tissue type composition percentage of teratomas generated from BulkRNAseq and CIBERSORTx deconvolution. FIG. 8F: Top 10 Enriched GO terms from significantly enriched genes (padj<0.05, L2FC > 1). FIG.8G: Top 10 Depleted GO terms from significantly depleted genes (padj<0.05, L2FC < -1).

[0023] FIGS. 9A-9G show long term maturation and characterization of neural enriched teratomas. FIG. 9A: Schematic depicting experimental workflow for neural lineage enrichment and long term maturation in miR9Target_4x teratomas. FIGS. 9B, 9D, & 9F: Growth curves for week 10 (FIG.9B), week 24 (FIG. 9D) and week 36 (FIG. 9F) teratomas. FIGS. 9C, 9E, & 9G: Hematoxylin and Eosin stain of representative AP20187 untreated and treated week 10 (FIG. 9C), week 24 (FIG. 9E) and week 36 (FIG. 9G) mir9Target_4x teratomas, along with Immunofluorescence stains for mature neuron markers TUJI or MAP2 and Glial marker GFAP.

[0024] FIGS. 10A-10H show miRNA 140 based suicide circuit enables enrichment of cartilage in-vivo. FIG. 10A: Schematic depicting experimental workflow for Chondrogenic MSC enrichment in miR140Target_4x teratomas. FIG. 10B: Percent change in tumor volume after 7 days of AP20187(n=4) or vehicle(n=3) treatment. FIG. IOC: Hematoxylin and Eosin stain of representative AP20187 untreated and treated mirl40Target_4x teratomas. FIG. 10D:Immunofluorescence stains from representative AP20187 untreated and treated mirl40Target_4x teratomas for articular cartilage structural proteins collagen 2 (COL2A1) and aggrecan (ACAN), counter stained with DAPI. FIG. 10E: SafraninO / Fast green immunohistological stain of cartilage in a AP20187 treated mirl40Target_4x teratoma. FIG. 10F: Tissue type composition percentage of teratomas generated from BulkRNAseq and CIBERSORTx deconvolution. FIG.10G: Top 10 Enriched GO terms from significantly enriched genes (padj<0.05, L2FC > 1). FIG.10H: Top 10 Depleted GO terms from significantly depleted genes (padj<0.05, L2FC < -1).

[0025] FIGS. 11A-11D show maturation and transplantation of sculpted cartilage. FIG. HA:Schematic depicting experimental workflow for maturation of miR140Target_4x sculpted teratomas. FIG. 11B: Schematic depicting experimental workflow for transplantation of cartilage from sculpted teratomas into nude rats. FIG. 11C: Immunofluorescence stain of chondrocytes after in vitro culture for collagen 2 and aggrecan. FIG. HD: Gross images of 24 week matured miR140Target_4x sculpted teratomas.

[0026] FIGS. 12A-12D show miRNA mediated suicide circuit confers cell type survival in vitro. FIG. 12A: Gel electrophoresis depicting the attR and attL recombination site amplicons post BXBl-mediated recombination into the AAVS1 locus for mirEmpty and mir9Target_lx cell lines. FIG. 12B: Scaled expression of various cell type specific miRNA Host Genes across teratoma cell types, generated from single nucleus sequencing data. FIG. 12C: Flow Cytometry detection of EGFP and Mcherry intensity in Undifferentiated, Day 3 and Day 7 differentiated neurons from mir9Target_4x, mir9Target_lx, and mirEmpty clonal lines. FIG. 12D: %of Maximum EGFP expression as quantified by Flow Cytometry of Undifferentiated, Day 3 and Day 7 differentiated neurons from mir9Target_4x, mir9Target_lx, and mirEmpty clonal lines.

[0027] FIGS. 13A-13K show the suicide circuit remained functional in vivo during prolonged differentiation of the teratomas. FIG. 13A: Schematic depicting experimental workflow for teratoma depletion in mirEmpty teratomas. FIGS. 13B-13D: Growth curves for (FIG. 13B)-AP20187 (n=4), (FIG. 13C) +AP20187 week 7 (n=3), and (FIG. 13D)+AP20187 week 10 (n=4) mirEmpty teratomas. FIGS. 13E-13G: Images of (FIG. 13E)-AP20187 (n=4), (FIG. 13F)+AP20187 week 7 (n=3), and (FIG. 13G)+AP20187 week 10 (n=4) mirEmpty teratomas upon harvest, with 1 Inch ruler marking for scale. FIG. 13H: Hematoxylin and Eosin stain of representative AP20187 untreated and treated mirEmpty teratomas. FIG. 131: Tissue type composition percentage of -AP20187 and +AP20187 week 10 mirEmpty teratomas generated from BulkRNAseq and CIBERSORTx deconvolution. FIG. 13J: Relative mRNA expression of neural markers MAP2, RBFOX3, PAX6, andNeuroDl in mir9Target_4x AP20187 treated teratomas (n=4) (normalized to mir9Target_4x AP20187 untreated teratomas n=4 ) as well as in mirEmpty AP20187 treated teratomas (n=4) (normalized to mirEmpty AP20187 untreated teratomas n=4). FIG. 13K: Relative mRNA expression of chondrogenic mesenchymal stem cell markers THY1, SOX9, and COL2A1 in mirl40Target_4x AP20187 treated teratomas (n=4) (normalized to mirl40Target_4x AP20187 untreated teratomas n=3) as well as in mirEmpty AP20187 treated teratomas (n=4) (normalized to mirEmpty AP20187 untreated teratomas n=3).

[0028] FIGS. 14A-14F show enrichment of neural lineage through in vivo sculpting with miR-9. FIGS. 14A-14B: Growth curves for -AP20187 (n=4) (FIG. 14A) and +AP20187 (n=4) (FIG.14B) mir9Target_4x teratomas. FIG. 14C: H& E sections of all -AP20187 mir9Target_4x teratomas. FIG. 14D: Immunofluorescence stains of all -AP20187 mir9Target_4x teratomas for mature neuron marker MAP2 and post mitotic neural marker neuron-specific P3-tubulin (TuJl), counter stained with DAPI. FIG. 14E: H& E sections of all +AP20187 mir9Target_4x teratomas.FIG. 14F: Immunofluorescence stains of all +AP20187 mir9Target 4x teratomas for mature neuron marker MAP2 and post mitotic neural marker neuron-specific |33-tubulin (TuJl), counter stained with DAPI.

[0029] FIGS. 15A-15G show in vivo sculpting allows for generation of macroscale cartilage.FIGS. 15A-15B: Growth curves for -AP20187 (n=3) (FIG. 15A) and +AP20187 (n=4) (FIG.15B) mirl40Target 4x teratomas. FIG. 15C: Image of one AP20187 untreated and treated teratoma each immediately post harvest. Red Arrows Point to examples of cartilage observed by eye. FIG. 15D: H& E sections of all -AP20187 mirl40Target_4x teratomas. FIG. 15E:Immunofluorescence stains from all -AP20187 mir!40Target_4x teratomas for articular cartilage structural proteins collagen 2 (COL2A1) and aggrecan (AC AN), counter stained with DAPI. FIG. 15F: H& E sections of all +AP20187 mirl40Target_4x teratomas. FIG. 15G:Immunofluorescence stains from all +AP20187 mirl40Target_4x teratomas for articular cartilage structural proteins collagen 2 (COL2A1) and aggrecan (AC AN), counter stained with DAPI.DETAILED DESCRIPTIONDefinitions

[0030] While various embodiments and aspects of the present invention are show n and described herein, it will be obvious to those skilled in the art that such embodiments and aspects are provided by way of example only. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein may be employed in practicing the invention.

[0031] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in the application including, without limitation, patents, patent applications, articles, books, manuals, and treatises are hereby expressly incorporated by reference in their entirety for any purpose.

[0032] The abbreviations used herein have their conventional meaning within the chemical and biological arts. The chemical structures and formulae set forth herein are constructed according to the standard rules of chemical valency known in the chemical arts.

[0033] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by a person of ordinary' skill in the art. See, e.g., Singleton et al., DICTIONARY OF MICROBIOLOGY AND MOLECULAR BIOLOGY 2nd ed., J. Wiley & Sons (New York. NY 1994); Sambrook et al., MOLECULAR CLONING, A LABORATORY MANUAL, Cold Springs Harbor Press (Cold Springs Harbor, NY 1989). Any methods, devices and materials similar or equivalent to those described herein can be used in the practice of this invention. The follow ing definitions are provided to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.

[0034] " Nucleic acid" refers to nucleotides (e.g., deoxy ribonucleotides or ribonucleotides) and polymers thereof in either single-, double- or multiple-stranded form, or complements thereof; or nucleosides (e.g., deoxyribonucleosides or ribonucleosides). In embodiments, “nucleic acid” does not include nucleosides. The terms “polynucleotide,” “oligonucleotide,” “oligo” or the like refer, in the usual and customary sense, to a linear sequence of nucleotides. The term “nucleoside” refers, in the usual and customary sense, to a glycosylamine including a nucleobase and a five-carbon sugar (ribose or deoxyribose). Non limiting examples, of nucleosides include cytidine, uridine, adenosine, guanosine, thymidine and inosine. The term “nucleotide” refers, inthe usual and customary sense, to a single unit of a polynucleotide, i.e., a monomer. Nucleotides can be ribonucleotides, deoxyribonucleotides, or modified versions thereof. Examples of polynucleotides contemplated herein include single and double stranded DNA, single and double stranded RNA, and hybrid molecules having mixtures of single and double stranded DNA and RNA. Examples of nucleic acid, e.g. polynucleotides contemplated herein include any types of RNA, e.g. mRNA, siRNA, miRNA, and guide RNA and any types of DNA, genomic DNA, plasmid DNA, and minicircle DNA, and any fragments thereof. The term “duplex” in the context of polynucleotides refers, in the usual and customary' sense, to double strandedness. Nucleic acids can be linear or branched. For example, nucleic acids can be a linear chain of nucleotides or the nucleic acids can be branched, e.g., such that the nucleic acids comprise one or more arms or branches of nucleotides. Optionally, the branched nucleic acids are repetitively branched to form higher ordered structures such as dendrimers and the like.

[0035] Nucleic acids, including e.g., nucleic acids with a phosphothioate backbone, can include one or more reactive moieties. As used herein, the term reactive moiety includes any group capable of reacting with another molecule, e.g., a nucleic acid or polypeptide through covalent, non-covalent or other interactions. By way of example, the nucleic acid can include an amino acid reactive moiety' that reacts with an amino acid on a protein or polypeptide through a covalent, non-covalent or other interaction.

[0036] The terms also encompass nucleic acids containing known nucleotide analogs or modified backbone residues or linkages, which are synthetic, naturally occurring, and non-naturally occurring, which have similar binding properties as the reference nucleic acid, and which are metabolized in a manner similar to the reference nucleotides. Examples of such analogs include, without limitation, phosphodiester derivatives including, e.g., phosphorami date, phosphorodiamidate. phosphorothioate (also known as phosphothioate having double bonded sulfur replacing oxygen in the phosphate), phosphorodithioate, phosphonocarboxylic acids, phosphonocarboxylates, phosphonoacetic acid, phosphonoformic acid, methyl phosphonate, boron phosphonate, or O-methylphosphoroamidite linkages (see Eckstein, OLIGONUCLEOTIDES AND ANALOGUES: A PRACTICAL APPROACH, Oxford University Press) as well as modifications to the nucleotide bases such as in 5-methyl cytidine or pseudouridine.; and peptide nucleic acid backbones and linkages. Other analog nucleic acids include those with positive backbones; non-ionic backbones, modified sugars, and non-ribose backbones (e g. phosphorodiamidate morpholino oligos or locked nucleic acids (LNA) as known in the art), including those described in U. S. Patent Nos. 5,235,033 and 5.034,506, and Chapters6 and 7, ASC Symposium Senes 580, CARBOHYDRATE MODIFICATIONS IN ANTISENSE RESEARCH, Sanghui & Cook, eds. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. Modifications of the ribose-phosphate backbone may be done for a variety of reasons, e.g., to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip. Mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made. In embodiments, the intemucleotide linkages in DNA are phosphodiester, phosphodiester derivatives, or a combination of both.

[0037] Nucleic acids can include nonspecific sequences. As used herein, the term "nonspecific sequence" refers to a nucleic acid sequence that contains a series of residues that are not designed to be complementary to or are only partially complementary' to any other nucleic acid sequence. By way of example, a nonspecific nucleic acid sequence is a sequence of nucleic acid residues that does not function as an inhibitory nucleic acid when contacted with a cell or organism.

[0038] A polynucleotide is typically composed of a specific sequence of four nucleotide bases: adenine (A); cytosine (C); guanine (G); and thymine (T) (uracil (U) for thymine (T) when the polynucleotide is RNA). Thus, the term “polynucleotide sequence” is the alphabetical representation of a polynucleotide molecule; alternatively, the term may be applied to the polynucleotide molecule itself. This alphabetical representation can be input into databases in a computer having a central processing unit and used for bioinformatics applications such as functional genomics and homology' searching. Polynucleotides may optionally include one or more non-standard nucleotide(s), nucleotide analog(s) and / or modified nucleotides.

[0039] The term “complement,” as used herein, refers to a nucleotide (e.g., RNA or DNA) or a sequence of nucleotides capable of base pairing with a complementary nucleotide or sequence of nucleotides. As described herein and commonly known in the art the complementary (matching) nucleotide of adenosine is thymidine and the complementary' (matching) nucleotide of guanosine is cytosine. Thus, a complement may include a sequence of nucleotides that base pair w ith corresponding complementary nucleotides of a second nucleic acid sequence. The nucleotides of a complement may partially or completely match the nucleotides of the second nucleic acid sequence. Where the nucleotides of the complement completely match each nucleotide of the second nucleic acid sequence, the complement forms base pairs with each nucleotide of thesecond nucleic acid sequence. Where the nucleotides of the complement partially match the nucleotides of the second nucleic acid sequence only some of the nucleotides of the complement form base pairs with nucleotides of the second nucleic acid sequence. Examples of complementary sequences include coding and a non-coding sequences, wherein the non-coding sequence contains complementary nucleotides to the coding sequence and thus forms the complement of the coding sequence. A further example of complementary sequences are sense and antisense sequences, wherein the sense sequence contains complementary nucleotides to the antisense sequence and thus forms the complement of the antisense sequence.

[0040] As described herein the complementarity of sequences may be partial, in which only some of the nucleic acids match according to base pairing, or complete, where all the nucleic acids match according to base pairing. Thus, two sequences that are complementary to each other, may have a specified percentage of nucleotides that are the same (i.e., about 60% identity, preferably 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity over a specified region).

[0041] The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function in a manner similar to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, y-carboxy glutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, i.e., an a carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions in a manner similar to a naturally occurring amino acid. The terms "non-natural ly occurring amino acid'’ and “unnatural amino acid” refer to amino acid analogs, synthetic amino acids, and amino acid mimetics which are not found in nature.

[0042] Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.

[0043] The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues, wherein the polymer may In embodiments be conjugated to a moiety that does not consist of amino acids. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers and non-naturally occurring amino acid polymers. A "fusion protein" refers to a chimeric protein encoding two or more separate protein sequences that are recombinantly expressed as a single moiety.

[0044] An amino acid or nucleotide base "position" is denoted by a number that sequentially identifies each amino acid (or nucleotide base) in the reference sequence based on its position relative to the N-terminus (or 5'-end). Due to deletions, insertions, truncations, fusions, and the like that must be considered when determining an optimal alignment, in general the amino acid residue number in a test sequence determined by simply counting from the N-terminus will not necessarily be the same as the number of its corresponding position in the reference sequence. For example, in a case where a variant has a deletion relative to an aligned reference sequence, there will be no amino acid in the variant that corresponds to a position in the reference sequence at the site of deletion. Where there is an insertion in an aligned reference sequence, that insertion will not correspond to a numbered amino acid position in the reference sequence. In the case of truncations or fusions there can be stretches of amino acids in either the reference or aligned sequence that do not correspond to any amino acid in the corresponding sequence.

[0045] The terms "numbered with reference to" or "corresponding to," when used in the context of the numbering of a given amino acid or polynucleotide sequence, refers to the numbering of the residues of a specified reference sequence when the given amino acid or polynucleotide sequence is compared to the reference sequence. An amino acid residue in a protein "corresponds" to a given residue when it occupies the same essential structural position within the protein as the given residue. One skilled in the art will immediately recognize the identity and location of residues corresponding to a specific position in a protein (e.g., MAP2) in other proteins with different numbering systems. For example, by performing a simple sequence alignment with a protein (e.g., MAP2) the identity and location of residues corresponding to specific positions of the protein are identified in other protein sequences aligning to the protein. For example, a selected residue in a selected protein corresponds to glutamic acid at position 138 when the selected residue occupies the same essential spatial or other structural relationship as a glutamic acid at position 138. In some embodiments, where a selected protein is aligned formaximum homology with a protein, the position in the aligned selected protein aligning with glutamic acid 138 said to correspond to glutamic acid 138. Instead of a primary sequence alignment, a three dimensional structural alignment can also be used, e.g., where the structure of the selected protein is aligned for maximum correspondence with the glutamic acid at position 138, and the overall structures compared. In this case, an amino acid that occupies the same essential position as glutamic acid 138 in the structural model is said to correspond to the glutamic acid 138 residue.

[0046] " Conservatively modified variants" applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, "conservatively modified variants" refers to those nucleic acids that encode identical or essentially identical amino acid sequences. Because of the degeneracy of the genetic code, a number of nucleic acid sequences will encode any given protein. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine. Thus, at every' position where an alanine is specified by a codon, the codon can be altered to any of the corresponding codons described wi thout altering the encoded polypeptide. Such nucleic acid variations are "silent variations," which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes every' possible silent variation of the nucleic acid. One of skill will recognize that each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG. which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, each silent variation of a nucleic acid which encodes a polypeptide is implicit in each described sequence.

[0047] As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the disclosure.

[0048] The following eight groups each contain amino acids that are conservative substitutions for one another:1) Alanine (A), Glycine (G);2) Aspartic acid (D), Glutamic acid (E);3) Asparagine (N), Glutamine (Q);4) Arginine (R), Lysine (K);5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V);6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W);7) Serine (S), Threonine (T); and8) Cysteine (C), Methionine (M)(see, e.g., Creighton, Proteins (1984)).

[0049] The terms "identical" or percent "identity," in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 60% identity, preferably 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection (see, e.g., NCBI web site http: / / www.ncbi.nlm.nih.gov / BLAST / or the like). Such sequences are then said to be "substantially identical." This definition also refers to, or may be applied to, the compliment of a test sequence. The definition also includes sequences that have deletions and / or additions, as well as those that have substitutions. As described below, the preferred algorithms can account for gaps and the like. Preferably, identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.

[0050] " Percentage of sequence identity" is determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide or polypeptide sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the totalnumber of positions in the window of comparison and multiplying the result by 100 to yield the percentage of sequence identity.

[0051] A "comparison window", as used herein, includes reference to a segment of any one of the number of contiguous positions selected from the group consisting of, e.g., a full length sequence or from 20 to 600, about 50 to about 200, or about 100 to about 150 amino acids or nucleotides in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman (1970) Adv. Appl. Math. 2:482c. by the homology alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol. 48:443, by the search for similarity method of Pearson and Lipman (1988) Proc. Nat’l. Acad. Sci. USA 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison. WI), or by manual alignment and visual inspection (see, e.g., Ausubel et al.. Current Protocols in Molecular Biology (1995 supplement)).

[0052] An example of an algorithm that is suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al. (1977) Nuc. Acids Res. 25:3389-3402, and Altschul et al. (1990) J. Mol. Biol. 215:403-410, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (http: / / www.ncbi.nlm.nih.gov / ). This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive-valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al., supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The w ord hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always > 0) and N (penalty' score for mismatching residues; always < 0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one ormore negative-scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, an expectation (E) or 10, M=5, N=-4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a word length of 3. and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff and Henikoff (1989) Proc. Natl. Acad. Sci. USA 89:10915) alignments (B) of 50, expectation (E) of 10, M=5, N=-4, and a comparison of both strands.

[0053] The BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see. e.g., Karlin and Altschul (1993) Proc. Natl. Acad. Sci. USA 90:5873-5787). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(N)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, more preferably less than about 0.01, and most preferably less than about 0.001.

[0054] An indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the antibodies raised against the polypeptide encoded by the second nucleic acid, as described below. Thus, a polypeptide is typically substantially identical to a second polypeptide, for example, where the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules or their complements hybridize to each other under stringent conditions, as described below. Yet another indication that two nucleic acid sequences are substantially identical is that the same primers can be used to amplify the sequence.

[0055] The phrase "specifically (or selectively) binds" to an antibody or "specifically (or selectively) immunoreactive with," when referring to a protein or peptide, refers to a binding reaction that is determinative of the presence of the protein, often in a heterogeneous population of proteins and other biologies. Thus, under designated immunoassay conditions, the specified antibodies bind to a particular protein at least two times the background and more typically more than 10 to 100 times background. Specific binding to an antibody under such conditions requires an antibody that is selected for its specificity for a particular protein. For example, polyclonalantibodies can be selected to obtain only a subset of antibodies that are specifically immunoreactive with the selected antigen and not with other proteins. This selection may be achieved by subtracting out antibodies that cross-react with other molecules. A variety of immunoassay formats may be used to select antibodies specifically immunoreactive with a particular protein. For example, solid-phase ELISA immunoassays are routinely used to select antibodies specifically immunoreactive with a protein (see, e.g., Harlow & Lane, Using Antibodies, A Laboratory Manual (1998) for a description of immunoassay formats and conditions that can be used to determine specific immunoreactivity).

[0056] A "ligand" refers to an agent, e g., a polypeptide or other molecule, capable of binding to a receptor or antibody, antibody variant, antibody region or fragment thereof.

[0057] Techniques for conjugating therapeutic agents to antibodies are well known (see, e.g., Amon et al., " Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy", in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Deliveiy”in Controlled Drug Delivery (2ndEd.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker. Inc. 1987); Thorpe, " Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review" in Monoclonal Antibodies ‘84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); and Thorpe et al., " The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates", Immunol. Rev., 62:183-98 (1982)). As used herein, the term “antibody-drug conjugate" or “ADC” refers to a therapeutic agent conjugated or otherwise covalently bound to to an antibody.

[0058] For specific proteins described herein, the named protein includes any of the protein’s naturally occurring forms, variants or homologs that maintain the protein transcription factor activity (e.g., within at least 50%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity compared to the native protein). In some embodiments, variants or homologs have at least 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g. a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring form. In other embodiments, the protein is the protein as identified by its NCBI sequence reference. In other embodiments, the protein is the protein as identified by its NCBI sequence reference, homolog or functional fragment thereof.

[0059] The term "gene" means the segment of DNA involved in producing a protein; it includes regions preceding and following the coding region (leader and trailer) as well as intervening sequences (introns) between individual coding segments (exons). The leader, thetrailer as well as the introns include regulatory elements that are necessary during the transcription and the translation of a gene. Further, a "protein gene product" is a protein expressed from a particular gene.

[0060] The terms "plasmid", "vector" or "expression vector" refer to a nucleic acid molecule that encodes for genes and / or regulatory elements necessary for the expression of genes.Expression of a gene from a plasmid can occur in cis or in trans. If a gene is expressed in cis. the gene and the regulatory elements are encoded by the same plasmid. Expression in trans refers to the instance where the gene and the regulatory' elements are encoded by separate plasmids.

[0061] The terms "transfection", "transduction", "transfecting" or "transducing" can be used interchangeably and are defined as a process of introducing a nucleic acid molecule or a protein to a cell. Nucleic acids are introduced to a cell using non-viral or viral-based methods. The nucleic acid molecules may be gene sequences encoding complete proteins or functional portions thereof. Non-viral methods of transfection include any appropriate transfection method that does not use viral DNA or viral particles as a delivery system to introduce the nucleic acid molecule into the cell. Exemplary non-viral transfection methods include calcium phosphate transfection, liposomal transfection, nucleofection, sonoporation, transfection through heat shock, magnetifection and electroporation. In some embodiments, the nucleic acid molecules are introduced into a cell using electroporation following standard procedures well know n in the art. For viral-based methods of transfection any useful viral vector may be used in the methods described herein. Examples for viral vectors include, but are not limited to retroviral, adenoviral, lentiviral and adeno-associated viral vectors. In some embodiments, the nucleic acid molecules are introduced into a cell using a retroviral vector following standard procedures well known in the art. The terms "transfection" or "transduction" also refer to introducing proteins into a cell from the external environment. Typically, transduction or transfection of a protein relies on attachment of a peptide or protein capable of crossing the cell membrane to the protein of interest. See, e.g., Ford et al. (2001) Gene Therapy 8:1-4 and Prochiantz (2007) Nat. Methods 4:119-20.

[0062] A "label" or a "detectable moiety" is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means. For example, useful labels include 32P, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and proteins or other entities which can be made detectable, e.g., by incorporating a radiolabel into a peptide or antibody specificallyreactive with a target peptide. Any appropriate method known in the art for conjugating an antibody to the label may be employed, e g., using methods described in Hermanson, Bioconjugate Techniques 1996, Academic Press, Inc., San Diego.

[0063] When the label or detectable moiety is a radioactive metal or paramagnetic ion, the agent may be reacted with another long-tailed reagent having a long tail with one or more chelating groups attached to the long tail for binding to these ions. The long tail may be a polymer such as a polylysine, polysaccharide, or other derivatized or derivatizable chain having pendant groups to which the metals or ions may be added for binding. Examples of chelating groups that may be used according to the disclosure include, but are not limited to, ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTP A), DOTA, NOTA, NETA, TETA, porphyrins, polyamines, crown ethers, bis-thiosemicarbazones, poly oximes, and like groups. The chelate is normally linked to the PSMA antibody or functional antibody fragment by a group, which enables the formation of a bond to the molecule with minimal loss of immunoreactivity and minimal aggregation and / or internal cross-linking. The same chelates, when complexed with non-radioactive metals, such as manganese, iron and gadolinium are useful for MRI, when used along with the antibodies and carriers described herein. Macrocyclic chelates such as NOTA, DOTA, and TETA are of use with a variety of metals and radiometals including, but not limited to, radionuclides of gallium, yttrium and copper, respectively. Other ring-type chelates such as macrocyclic polyethers, which are of interest for stably binding nuclides, such as223Ra for RAIT may be used. In certain embodiments, chelating moieties may be used to attach a PET imaging agent, such as an A1-18F complex, to a targeting molecule for use in PET analysis.

[0064] The term ‘‘small molecule’' is used in accordance with its well understood meaning and refers to a low molecular weight organic compound that may regulate a biological process. In embodiments, the small molecule is a compound that weighs less than 1000 daltons. In embodiments, the small molecule is a compound that weighs less than 900 daltons. In embodiments, the small molecule weighs less than 800 daltons. In embodiments, the small molecule weighs less than 700 daltons. In embodiments, the small molecule weighs less than 600 daltons. In embodiments, the small molecule weighs less than 500 daltons. In embodiments, the small molecule weighs less than 450 daltons. In embodiments, the small molecule weighs less than 400 daltons. In embodiments, the small molecule compound is a drug compound. In embodiments, the small molecule compound is AP20187, rimiducid (AP1903), AP21967,rapamycin, gibberellic acid, tamoxifen, lenalidomide, pomalidomide, A1331852, 1155463, or TMP-POM-7c.

[0065] The term “inducible dimerizing apoptotic protein” is used herein according to its plain and ordinary meaning and refers to a protein that induces apoptosis upon dimerization in the presence of a compound (e.g., an exogenous compound). In embodiments, the inducible dimerizing apoptotic protein includes a compound-inducible dimerizing domain and an apoptotic domain. In embodiments, the inducible dimerizing apoptotic protein is inactive in the absence of the compound. In embodiments, the compound is capable of inducing dimerization of a first compound-inducible dimerizing domain of a first inducible dimerizing apoptotic protein and a second compound-inducible dimerizing domain of a second inducible dimerizing apoptotic protein, thereby producing an induced dimerized apoptotic protein complex, wherein the induced dimerized apoptotic protein complex includes the first inducible dimerizing apoptotic protein, the second inducible dimerizing apoptotic protein and the compound. In embodiments, the compound induces dimerization of a first compound-inducible dimerizing domain of a first inducible dimerizing apoptotic protein and a second compound-inducible dimerizing domain of a second inducible dimerizing apoptotic protein by binding to the first compound-inducible dimerizing domain and the second compound-inducible dimerizing domain.

[0066] The term “induced dimerized apoptotic protein complex” is used herein according to its plain and ordinary meaning and refers to a complex comprising a first inducible dimerizing apoptotic protein dimerized to a second inducible dimerizing apoptotic protein via a compound. In embodiments, the induced dimerized apoptotic protein complex is active in the presence of the compound. In embodiments, the induced dimerized apoptotic protein complex is capable of inducing apoptosis in a cell. In embodiments, the induced dimerized apoptotic protein complex includes the first inducible dimerizing apoptotic protein, the second inducible dimerizing apoptotic protein, and the compound.

[0067] The term “microRNA” or “miRNA” is used herein according to its plain and ordinary meaning and refers to a small non-coding RNA sequence that regulates gene expression post-transcriptionally. In embodiments, the miRNA is about 20 nucleotides to about 26 nucleotides in length. In embodiments, the miRNA binds to a complementary sequence in a messenger RNA (mRNA) to inhibit translation or promote degradation of the mRNA. In embodiments, the miRNA binds to an miRNA-binding sequence. In embodiments, the miRNA hybridizes hybridizes to a miRNA-binding sequence. In embodiments, the miRNA is expressedendogenously by a cell. In embodiments, the miRNA is a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA. In embodiments, the miRNA is binding miR-192, miR-194, miR-122. miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-216a, miR-133a, miR-17, miR-125, miR-338, miR-128, miR-204, miR-211, miR-203, miR-96, miR-206, miR-145, miR-143, miR-208a, miR-140, miR-199, miR-214, miR-126, miR-451, miR-223, miR-130a, miR-142. miR-181a, miR-191. miR-148a, miR-7, miR-10, miR-125b, miR-132, miR-212, miR-137, miR-184, miR-200, miR-18, miR-21, or miR-302a. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO: 11. SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16. SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO 81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95. SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO 98, SEQ ID NO:99, SEQ ID NO:100, SEQ ID NO:10L SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, or SEQ ID NO: 112. In embodiments, the miRNA is a non-endogenous miRNA. In embodiments, the miRNA is not endogenously expressed by a cell. miRNA are well known in the art (See, e.g., Alberti et al., Development, 2017:144:2548-59; Zeng, Oncogene, 2006;25:6156-62; and Ivey et al.. Cold Spring Harb Perspect Biol, 2015;7(7):a008144, each of which is incorporated herein by reference in its entirety and for all purposes).

[0068] The term ‘‘non-endogenous miRNA,'’ also known as “artificial microRNA’' or “amiRNA,” is used herein according to its plain and ordinary meaning and refers to a miRNA sequence that is not endogenous and not endogenously expressed by a cell. In embodiments, the non-endogenous miRNA is about 20 nucleotides to about 26 nucleotides in length. In embodiments, the non-endogenous miRNA binds to a complementary sequence in a messenger RNA (mRNA) to inhibit translation or promote degradation of the mRNA. In embodiments, the non-endogenous miRNA binds to an miRNA-binding sequence. In embodiments, the non-endogenous miRNA hybridizes to an miRNA-binding sequence. In embodiments, the non-endogenous miRNA does not exist in nature. In embodiments, the non-endogenous miRNA is a non-natural miRNA. In embodiments, the non-endogenous miRNA is a recombinant miRNA. In embodiments, the non-endogenous miRNA is engineered to be expressed in a cell. In embodiments, the non-endogenous miRNA is an inducible miRNA. In embodiments, the non-endogenous miRNA is encoded by an exogenous nucleic acid construct introduced into a cell. In embodiments, the non-endogenous miRNA is designed to target the nucleic acid sequences provided herein including embodiments thereof. In embodiments, the non-endogenous miRNA does not target an endogenous gene in the cell. In embodiments, the non-endogenous miRNA is inserted in a cell-specific or tissue-specific gene. In embodiments, the non-endogenous miRNA is inserted into the 3' untranslated region (3' UTR) of a gene. In embodiments, the non-endogenous miRNA is inserted into the 3' UTR of a cell-specific or tissue-specific gene. In embodiments, expression of the non-endogenous miRNA is controlled by expression of the cellspecific or tissue-specific gene. In embodiments, the cell-specific gene or tissue-specific gene is OCT4, SOX2, KLF4, c-MYC, PAX6, GLI3, TBR1, CTIP2, TMDB15A, NNAT, GFAP, AQP4, EOMES, NEURODI, SATB2, or BRN2. Non-endogenous miRNA or amiRNA are well known in the art (See, e.g., Hu et al., Mol Biotechnol, 2010;46(l):34-40 and Ross et al., Sei Transl Med, 2025;17(792):eadq3614, each of which is incorporated herein by reference in its entirety and for all purposes). In embodiments, non-endogenous miRNA can be inserted into the genome of a cell or expressed in a cell using known techniques in the art (e.g., exon scaffolds). The methods and techniques described in Hu et al., 2010 and Ross et al., 2025 may be used to express the non-endogenous miRNA described herein.

[0069] The term ’microRN A-binding sequence"’ or "‘miRNA-binding sequence” is used herein according to its plain and ordinary meaning and refers to a nucleotide sequence capable of being binding amicroRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to the miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to the miRNA under biological conditions (e g., wtihin a cell). In embodiments, the miRNA-binding sequence is substantially complementary to the miRNA. In embodiments, the miRNA-binding sequence is complementary to the miRNA. In embodiments, the miRNA is expressed by a cell. In embodiments, the miRNA is an endogenous miRNA. In embodiments, the binding of an miRNA to a miRNA-binding sequence blocks translation of the nucleic acid. In embodiments, the binding of an miRNA to a miRNA-binding sequence blocks translation of the inducible dimerizing apoptotic protein. In embodiments, expression of the inducible dimerizing apoptoticprotein is blocked via miRNA silencing. In embodiments, the miRNA-binding sequence is located in the 3' untranslated region (UTR) of the nucleic acid. In embodiments, the microRNA is anon-endogenous microRNA (e.g., amiRNA). In embodiments, the miRNA-binding sequence includes the nucleotide sequence of anyone of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21. SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44. SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO 47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO 67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72. The nucleic acid compositions, cellular compositions, and methods of use thereof may include miRNA-binding sequences that are complementary to any of the miRNAs described in Alberti & Cochella, Development, 2017, 144, 2548-59; Zeng et al., Oncogene 2006, 25, 6156-62; and Ivey & Srivastava, Cold Spring Harb Perspect Biol, 2015, 7, a008144, each of which is incorporated herein in its entirety and for all purposes.

[0070] The term "‘compound-inducible dimerizing domain” is used herein according to its plain and ordinary meaning and refers to protein domain that is capable of binding to a compound (e.g., an exogenous compound) as set forth herein. In embodiments, the compound-inducible dimerizing domain is inactive in the absence of the compound. In embodiments, a first compound-inducible dimerizing domain binds the compound to promote dimerization with a second compound-inducible dimerizing domain. In embodiments, the compound-inducible dimerizing domain includes a compound-binding domain. In embodiments, the compound-inducible dimerizing domain is capable of forming a homodimer or heterodimer in the presence of the compound. In embodiments, the compound-inducible dimerizing domain includes a drug-mediated dimerization version B (DmrB) domain, a FK506-binding protein (FKBP) domain, a FKBP-rapamycin-binding (FRB) domain, a gibberellin-responsive receptor domain, a tamoxifen-responsive estrogen receptor domain, a cereblon-binding domain, a B-cell lymphoma (Bel) interaction domain, a dihydrofolate reductase domain, or variants thereof. In embodiments, the FKBP domain includes an FKBP 12 domain or a variant thereof. In embodiments, the FRB domain includes a FKBP-rapamycin-binding domain or a variant thereof. In embodiments, thegibberellin-responsive receptor domain includes a Gibberellin Insensitive (GAI) domain or a Gibberellin Insensitive Dwarf 1 (GID1) domain or a variant thereof. In embodiments, the tamoxifen-responsive estrogen receptor domain includes an ERT2 domain or a variant thereof. In embodiments, the cereblon-binding domain includes a CRBN domain or a CRBN-IZF3 domain or a variant thereof. In embodiments, the B-cell lymphoma (Bel) interaction domain includes a Bcl-XL domain or a pro-apoptotic domain Bim, or variants thereof. In embodiments, the dihydrofolate reductase domain includes a DHFR domain or a variant thereof.

[0071] The term “apoptotic domain’’ is used herein according to its plain and ordinary meaning and refers to a protein domain that is capable of inducing apoptosis. In embodiments, the apoptotic domain activates an apoptotic signaling pathway when brought into proximity with another apoptotic domain. In embodiments, the apoptotic domain includes a death domain or a death effector domain. In embodiments, the apoptotic domain is capable of initiating programmed cell death when part of a dimerized complex. In embodiments, the apoptotic domain is capable of initiating programmed cell death when dimerized. In embodiments, the apoptotic domain includes a caspase catalytic domain. In embodiments, the apoptotic domain includes a caspase protein, a tumor necrosis factor (TNF) protein, a CD95 ligand protein, a Fas ligand protein, or a TNF-related apoptosis-inducing ligand (TRAIL) protein, or a variant thereof. In embodiments, the apoptotic domain includes a caspase-3 protein, a caspase-8 protein, a caspase-9 protein, or a variant thereof. In embodiments, the apoptotic domain includes a TNF-a protein or a TNF-P protein or a variant thereof. In embodiments, the apoptotic domain includes a CD95-L protein or a variant thereof. In embodiments, the apoptotic domain includes a Fas-L protein or a variant thereof. In embodiments, the apoptotic domain includes a TRAIL protein or a variant thereof.

[0072] The term "‘organoid” is used herein according to its plain and ordinary meaning and refers to a three-dimensional mass of cells grown in vitro. In embodiments, the organoid mimics at least one structural or functional characteristic of an organ or tissue. In embodiments, the organoid includes cells that have undergone differentiation under conditions promoting tissuespecific organization. In embodiments, the organoid includes multiple cell types arranged in a spatial organization resembling an in vivo tissue. In embodiments, the organoid exhibits cytoarchitecture, signaling interactions, or physiological functions characteristic of the corresponding organ or tissue. In embodiments, the organoid is cultured in a matrix or scaffold that supports three-dimensional growth. In embodiments, the organoid is generated under conditions that promote lineage-specific differentiation. In embodiments, the organoid includesrecombinant cells. In embodiments, each recombinant cell within the organoid includes the nucleic acid provided herein including embodiments thereof. In embodiments, the organoid includes an acinar cell, an adipogenic mesenchymal stem cell, an adipogenic fibroblast, an airw ay epithelial cell, a bipolar cell, a chondrocyte, a chondrogenic mesenchymal stem cell, a chondrogenic fibroblast, a choroid plexus cell, a cycling mesenchymal stem cell, a cycling fibroblast, a cycling progenitor cell, a definitive endoderm cell, a differentiating excitatory neuron, a differentiating inhi bi lory neuron, a dopaminergic neuron, an early differentiating neuron, an early excitatory neuron, an early neuron, an endothelial cell, an enteric neuron, an enterocyte progenitor cell, an ependymal cell, an ependymal precursor cell, an ependymal-like cell, an embryonic stem cell, a foregut epithelial cell, a foveolar cell, a goblet cell, a hematopoietic stem cell, an immune cell, an inhibitor}' neuron, an intermediate progenitor cell, a kidney progenitor cell, a lung epithelial progenitor cell, a macrophage, a melanoblast, a melanocyte, a meningeal cell, a midgut epithelial cell, a hindgut epithelial cell, a mesenchymal stem cell, a fibroblast, a muscle progenitor cell, a myofibroblast, a nephron progenitor cell, a neural precursor cell, a neuroblast, a neuroectoderm cell, a neuroendocrine cell, an optic cup cell, a pericyte, a podocyte, a pre-oligodendrocyte progenitor cell, an oligodendrocyte progenitor cell, a radial glia cell, a retinal epithelial cell, a retinal ganglion cell, a retinal interneuron, a retinal neuron, a retinal pigment epithelial cell, a retinal progenitor cell, a radial glia astrocyte cell, an S-shaped body cell, a Schwann cell, a skeletal muscle cell, a cardiac muscle cell, a smooth muscle cell, a suprabasal cell, and / or a trachea basal cell. In embodiments, the organoid includes a OCT4-expressing cell, a SOX2-expressing cell, a KLF4-expressing cells, a c-MYC-expressing cell, a PAX6-expressing cell, a GLI3 -expressing cell, a TBR1 -expressing cell, CTIP2-expressing cell, a TMDB15A-expressing cell. aNNAT-expressing cell, a GFAP-expressing cell, an AQP4-expressing cell, an EOMES-expressing cell, a NEURODI -expressing cell, a SATB2-expressing cell, or a BRN2-expressing cell. Organoids are well known in the art (See, e.g., Gordon et al., Nat Neurosci, 2021;24:331-42 and Liu et al., Stem Cell Reports, 2023;18(12):2464-81, each of which is incorporated herein by reference in its entirety and for all purposes). The mass of recombinant cells (e.g., organoids) described herein may include any of the cells described in Gordon et al., 2021 and Liu et al., 2023.

[0073] The term “teratoma” is used herein according to its plain and ordinary meaning and refers to a three-dimensional mass of cells including multiple cell types. In embodiments, the cells within the teratoma originate from at least two embiyonic germ layers. In embodiments, the embryonic germ layer is ectoderm, mesoderm, and / or endoderm. In embodiments, the teratomaincludes cell types from all three germ layers, including ectoderm, mesoderm, and endoderm. In embodiments, the teratoma is formed by the differentiation of pluripotent stem cells in vivo. In embodiments, the teratoma exhibits vascularization and local tissue organization. In embodiments, the teratoma is generated by administereing pluripotent stem cells to a subject. In embodiments, the subject is anon-human animal. In embodiments, the subject is an immunodeficient, non-human animal. In embodiments, the teratoma includes recombinant cells. In embodiments, each recombinant cell within the teratoma includes the nucleic acid provided herein including embodiments thereof. In embodiments, the teratoma includes an acinar cell, an adipogenic mesenchymal stem cell, an adipogenic fibroblast, an airway epithelial cell, a bipolar cell, a chondrocyte, a chondrogenic mesenchymal stem cell, a chondrogemc fibroblast, a choroid plexus cell, a cycling mesenchymal stem cell, a cycling fibroblast, a cycling progenitor cell, a definitive endoderm cell, a differentiating excitatory' neuron, a differentiating inhibitory' neuron, a dopaminergic neuron, an early differentiating neuron, an early excitatory neuron, an early neuron, an endothelial cell, an enteric neuron, an enterocyte progenitor cell, an ependymal cell, an ependymal precursor cell, an ependymal-like cell, an embryonic stem cell, a foregut epithelial cell, a foveolar cell, a goblet cell, a hematopoietic stem cell, an immune cell, an inhibitory neuron, an intermediate progenitor cell, a kidney progenitor cell, a lung epithelial progenitor cell, a macrophage, a melanoblast, a melanocyte, a meningeal cell, a midgut epithelial cell, a hindgut epithelial cell, a mesenchymal stem cell, a fibroblast, a muscle progenitor cell, a myofibroblast, a nephron progenitor cell, a neural precursor cell, a neuroblast, a neuroectoderm cell, a neuroendocrine cell, an optic cup cell, a pericyte, a podocyte, a pre-oligodendrocyte progenitor cell, an oligodendrocyte progenitor cell, a radial glia cell, a retinal epithelial cell, a retinal ganglion cell, a retinal interneuron, a retinal neuron, a retinal pigment epithelial cell, a retinal progenitor cell, a radial glia astrocyte cell, an S-shaped body cell, a Schwann cell, a skeletal muscle cell, a cardiac muscle cell, a smooth muscle cell, a suprabasal cell, and / or a trachea basal cell. In embodiments, the organoid includes a OCT4-expressing cell, a SOX2-expressing cell, a KLF4-expressing cells, a c-MYC -expressing cell, a PAX6-expressing cell, a GLI3 -expressing cell, a TBR1 -expressing cell, CTIP2-expressing cell, a TMDB15A-expressing cell, aNNAT-expressing cell, a GF AP -expressing cell, an AQP4-expressing cell, an EOMES -expressing cell, a NEURODI -expressing cell, a SATB2-expressing cell, or a BRN2-expressing cell. Teratomas are well known in the art (See, e.g., McDonald et al., Cell, 2020;183(5):1402-19 and Liu et al., Stem Cell Reports, 2023;18(12):2464-81, each of which is incorporated herein by reference in itsentirety and for all purposes). The mass of recombinant cells (e.g., teratomas) described herein may include any of the cells described in McDonald et al., 2020 or Liu et al., 2023.

[0074] The term “AAVS1 locus” or '‘adeno-associated virus integration site 1 locus” is used herein according to its plain and ordinary meaning and refers to a genomic site within a cell that is commonly used as a safe harbor locus for targeted integration of transgenes. In embodiments, the AAVS1 locus is located on chromosome 19. In embodiments, the AAVS1 locus is located within the PPP1R12C gene region. In embodiments, the AAVS1 locus allows for stable expression of an integrated nucleic acid without disrupting essential endogenous gene function. In embodiments, the AAVS1 locus is targeted using site-specific nucleases, such as zinc finger nucleases, TALENs, or CRISPR-Cas systems. In embodiments, the AAVS1 locus is used for insertion of a suicide gene circuit, a reporter gene, or other genetic elements for controlled expression in a cell. In embodiments, the AAVS1 locus is used for inseration of the nucleic acid provided herein including embodiments thereof within the genome of a cell.

[0075] " Contacting" is used in accordance with its plain ordinary meaning and refers to the process of allowing at least two distinct species (e.g. antibodies and antigens) to become sufficiently proximal to react, interact, or physically touch. It should be appreciated, however, that the resulting reaction product can be produced directly from a reaction between the added reagents or from an intermediate from one or more of the added reagents which can be produced in the reaction mixture.

[0076] The term "contacting" may include allowing two species to react, interact, or physically touch, wherein the two species may be, for example, a pharmaceutical composition as provided herein and a cell. In embodiments contacting includes, for example, allowing a pharmaceutical composition as described herein to interact with a cell.

[0077] A "cell" as used herein, refers to a cell carrying out metabolic or other function sufficient to preserve or replicate its genomic DNA. A cell can be identified by well-known methods in the art including, for example, presence of an intact membrane, staining by a particular dye, ability’ to produce progeny or, in the case of a gamete, abi I i ty to combine with a second gamete to produce a viable offspring. Cells may include prokary otic and eukary otic cells. Prokaryotic cells include but are not limited to bacteria. Eukaryotic cells include, but are not limited to, yeast cells and cells derived from plants and animals, for example mammalian, insect (e.g., spodoptera) and human cells.

[0078] The term "recombinant" when used with reference, e.g., to a cell, nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified. Thus, for example, recombinant cells express genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed or not expressed at all. Transgenic cells and plants are those that express a heterologous gene or coding sequence, typically as a result of recombinant methods.

[0079] The term "isolated", when applied to a nucleic acid or protein, denotes that the nucleic acid or protein is essentially free of other cellular components with which it is associated in the natural state. It can be, for example, in a homogeneous state and may be in either a dry or aqueous solution. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. A protein that is the predominant species present in a preparation is substantially purified.

[0080] The term "heterologous" when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences from unrelated genes arranged to make a new functional nucleic acid, e.g.. a promoter from one source and a coding region from another source. Similarly, a heterologous protein indicates that the protein comprises two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).

[0081] The term "exogenous" refers to a molecule or substance (e.g., a compound, nucleic acid or protein) that originates from outside a given cell or organism. For example, an "exogenous promoter" as referred to herein is a promoter that does not originate from the cell or organism it is expressed by. Conversely, the term "endogenous" or "endogenous promoter" refers to a molecule or substance that is native to, or originates within, a given cell or organism.

[0082] As defined herein, the term "inhibition", "inhibit", "inhibiting" and the like in reference to cell proliferation (e.g.. cancer cell proliferation) means negatively affecting (e.g., decreasing proliferation) or killing the cell. In some embodiments, inhibition refers to reduction of a disease or symptoms of disease (e.g., cancer, cancer cell proliferation). Thus, inhibition includes, at leastin part, partially or totally blocking stimulation, decreasing, preventing, or delaying activation, or inactivating, desensitizing, or down-regulating signal transduction or enzymatic activity or the amount of a protein (e.g. a cancer-associated protein). Similarly an "inhibitor" is a compound or protein that inhibits a receptor or another protein, e.g.,, by binding, partially or totally blocking, decreasing, preventing, delaying, inactivating, desensitizing, or down-regulating activity (e.g., a receptor activity or a protein activity).

[0083] The term "expression" includes any step involved in the production of the polypeptide including, but not limited to, transcription, post-transcriptional modification, translation, post-translational modification, and secretion. Expression can be detected using conventional techniques for detecting protein (e.g., ELISA, Western blotting, flow cytometry, immunofluorescence, immunohistochemistry, etc.).

[0084] “Biological sample” or “sample” refer to materials obtained from or derived from a subject or patient. A biological sample includes sections of tissues such as biopsy and autopsy samples, and frozen sections taken for histological purposes. Such samples include bodily fluids such as blood and blood fractions or products (e.g., serum, plasma, platelets, red blood cells, and the like), sputum, tissue, cultured cells (e.g., primary cultures, explants, and transformed cells) stool, urine, synovial fluidjoint tissue, synovial tissue, synoviocytes, fibroblast-like synoviocytes, macrophage-like synoviocytes, immune cells, hematopoietic cells, fibroblasts, macrophages, T cells, etc. A biological sample is typically obtained from a eukaryotic organism, such as a mammal such as a primate e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat, mouse; rabbit; or a bird; reptile; or fish.

[0085] A “control” or “standard control” refers to a sample, measurement, or value that serves as a reference, usually a known reference, for comparison to a test sample, measurement, or value. For example, a test sample can be taken from a patient suspected of having a given disease (e.g. cancer) and compared to a known normal (non-diseased) individual (e.g. a standard control subject). A standard control can also represent an average measurement or value gathered from a population of similar individuals (e.g. standard control subjects) that do not have a given disease (i.e. standard control population), e.g., healthy individuals with a similar medical background, same age, weight, etc. A standard control value can also be obtained from the same individual, e.g. from an earlier-obtained sample from the patient prior to disease onset. For example, a control can be devised to compare therapeutic benefit based on pharmacological data (e.g., halflife) or therapeutic measures (e.g., comparison of side effects). Controls are also valuable fordetermining the significance of data. For example, if values for a given parameter are widely variant in controls, variation in test samples will not be considered as significant. One of skill will recognize that standard controls can be designed for assessment of any number of parameters (e.g. RNA levels, protein levels, specific cell ty pes, specific bodily fluids, specific tissues, etc).

[0086] One of skill in the art will understand which standard controls are most appropriate in a given situation and be able to analyze data based on comparisons to standard control values. Standard controls are also valuable for determining the significance (e.g. statistical significance) of data. For example, if values for a given parameter are widely variant in standard controls, variation in test samples will not be considered as significant.

[0087] It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview^ of this application and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety’ for all purposes.NUCLEIC ACID COMPOSITIONS

[0088] Provided herein are, inter alia, nucleic acid compositions including an inducible dimerizing apoptotic protein-encoding sequence and a miRNA-binding sequence. In embodiments, the nucleic acids provided herein including embodiments thereof are, inter alia, useful for selective, compound-induced activation of apoptosis in a mass of cells or a multilineage tissue (e.g., teratoma). In embodiments, the miRNA-binding sequences are useful for preventing apoptosis of a subpopulation of cells in the mass of cells or multi-lineage tissue based on endogenous expression of miRNA in the subpopulation of cells.

[0089] Thus, in an aspect is provided a nucleic acid including a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein includes a compound-inducible dimerizing domain and an apoptotic domain.

[0090] In embodiments, the nucleic acid includes from 5' to 3', the inducible dimerizing apoptotic protein and the first microRNA (miRNA)-binding sequence.

[0091] In embodiments, the nucleic acid includes a second miRNA-binding sequence. In embodiments, the nucleic acid includes a third miRNA-binding sequence. In embodiments, thenucleic acid includes a fourth miRNA-binding sequence. In embodiments, the nucleic acid further includes a second miRNA-binding sequence, a third miRNA-binding sequence, and a fourth miRNA-binding sequence. In embodiments, the nucleic acid includes a first miRNA-binding sequence, a second miRNA-binding sequence, a third miRNA-binding sequence, and a fourth miRNA-binding sequence.

[0092] In embodiments, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence independently are the same as the first miRNA-binding sequence. In embodiments, the second miRNA-binding sequence is the same as the first miRNA-binding sequence. In embodiments, the third miRNA-binding sequence is the same as the first miRNA-binding sequence. In embodiments, the fourth miRNA-binding sequence is the same as the first miRNA-binding sequence. In embodiments, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence are the same as the first miRNA-binding sequence.

[0093] In embodiments, the nucleic acid includes from 5' to 3', the inducible dimerizing apoptotic protein, the first microRNA (miRNA)-binding sequence, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence.

[0094] In embodiments, the compound is a small molecule compound. In embodiments, the small molecule is a drug compound. In embodiments, the drug compound is AP20187, rimiducid (AP1903), AP21967, rapamycin, gibberellic acid, tamoxifen, lenalidomide, pomalidomide, A1331852, A-1155463, or TMP-POM-7c. In embodiments, the drug compound is AP20187. In embodiments, the drug compound is rimiducid (AP1903). In embodiments, the drug compound is AP21967. In embodiments, the drug compound is rapamycin. In embodiments, the drug compound is gibberellic acid. In embodiments, the drug compound is tamoxifen. In embodiments, the drug compound is lenalidomide. In embodiments, the drug compound is pomalidomide. In embodiments, the drug compound is A1331852. In embodiments, the drug compound is A-1155463. In embodiments, the drug compound is TMP-POM-7c.

[0095] In embodiments, the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain, a FK506-binding protein (FKBP) domain, a FKBP-rapamycin-binding (FRB) domain, a gibberellin-responsive receptor domain, a tamoxifenresponsive estrogen receptor domain, a cereblon-binding domain, a B-cell lymphoma (Bel) interaction domain, or a dihydrofolate reductase domain. In embodiments, the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain. Inembodiments, the compound-inducible dimerizing domain is a FK506-binding protein (FKBP) domain. In embodiments, the compound-inducible dimerizing domain is a FKBP-rapamycin-binding (FRB) domain. In embodiments, the compound-inducible dimerizing domain is a gibberellin-responsive receptor domain. In embodiments, the compound-inducible dimerizing domain is a tamoxifen-responsive estrogen receptor domain. In embodiments, the compound-inducible dimerizing domain is a cereblon-binding domain. In embodiments, the compound-inducible dimerizing domain is a B-cell lymphoma (Bel) interaction domain. In embodiments, the compound-inducible dimerizing domain is a dihydrofolate reductase domain.

[0096] In embodiments, the compound is AP20187 and the compound-inducible dimerizing domain is a DmrB domain. In embodiments, the compound is rimiducid (AP1903) and the compound-inducible dimerizing domain is an FKBP 12 domain. In embodiments, the compound is AP21967 and the compound-inducible dimerizing domain is an FKBP-rapamycin-binding (FRB) domain. In embodiments, the compound is rapamycin and the compound-inducible dimerizing domain is an FKBP-rapamycin-binding (FRB) domain. In embodiments, the compound is gibberellic acid and the compound-inducible dimenzing domain is a Gibberellin Insensitive (GAI) domain or a Gibberellin Insensitive Dwarf 1 (GID1) domain. In embodiments, the compound is tamoxifen and the compound-inducible dimerizing domain is an ERT2 domain. In embodiments, the compound is lenalidomide and the compound-inducible dimerizing domain is a CRBN domain or a CRBN-IZF3 domain. In embodiments, the compound is pomalidomide and the compound-inducible dimerizing domain is a CRBN domain or a CRBN-IZF3 domain. In embodiments, the compound is A1331852 and the compound-inducible dimerizing domain is a B-cell lymphoma (Bel) domain or a pro-apoptotic domain Bim. In embodiments, the compound is A-1155463 and the compound-inducible dimerizing domain is a B-cell lymphoma (Bel) domain or a pro-apoptotic domain Bim. In embodiments, the compound is TMP-POM-7c and the compound-inducible dimerizing domain is a dihydrofolate reductase (DHFR) domain. In embodiments, the FKBP domain includes an FKBP 12 domain or a variant thereof. In embodiments, the FRB domain includes a FKBP-rapamycin-binding domain or a variant thereof. In embodiments, the gibberellin-responsive receptor domain includes a Gibberellin Insensitive (GAI) domain or a Gibberellin Insensitive Dwarf 1 (GID1) domain or a variant thereof. In embodiments, the gibberellin-responsive receptor domain includes a Gibberellin Insensitive (GAI) domain or a variant thereof. In embodiments, the gibberellin-responsive receptor domain includes a Gibberellin Insensitive Dwarf 1 (GID1) domain or a variant thereof. In embodiments, the tamoxifen-responsive estrogen receptor domain includes an ERT2 domainor a variant thereof. In embodiments, the cereblon-binding domain includes a CRBN domain or a CRBN-IZF3 domain or a variant thereof. In embodiments, the cereblon-binding domain includes a CRBN domain or a variant thereof. In embodiments, the cereblon-binding domain includes a CRBN-IZF3 domain or a variant thereof. In embodiments, the B-cell lymphoma (Bel) interaction domain includes a Bcl-XL domain or a pro-apoptotic domain Bim, or variants thereof. In embodiments, the B-cell lymphoma (Bel) interaction domain includes a Bcl-XL domain or variants thereof. In embodiments, the B-cell lymphoma (Bel) interaction domain includes a pro-apoptotic domain Bim or variants thereof. In embodiments, the dihydrofolate reductase domain includes a DHFR domain or a variant thereof.

[0097] In embodiments, the miRNA-binding sequence is capable of binding a non-endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of binding an endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of binding a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, or a cartilage miRNA a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA. In embodiments, the miRNA-binding sequence is capable of binding a hepatic miRNA. In embodiments, the miRNA-binding sequence is capable of binding a pancreatic miRNA. In embodiments, the miRNA-binding sequence is capable of binding a cardiac muscle miRNA. In embodiments, the miRNA-binding sequence is capable of binding a neural miRNA. In embodiments, the miRNA-binding sequence is capable of binding a glial miRNA. In embodiments, the miRNA-binding sequence is capable of binding a skeletal muscle miRNA. In embodiments, the miRNA-binding sequence is capable of binding a lung miRNA. In embodiments, the miRNA-binding sequence is capable of binding a cartilage miRNA. In embodiments, the miRNA-binding sequence is capable of binding a bone miRNA. In embodiments, the miRNA-binding sequence is capable of binding a vascular smooth muscle miRNA. In embodiments, the miRNA-binding sequence is capable of binding an endothelial miRNA. In embodiments, the miRNA-binding sequence is capable of binding a hematopoietic miRNA. In embodiments, the miRNA-binding sequence is capable of binding a myeloid miRNA. In embodiments, the miRNA-binding sequence is capable of binding a pluripotent stem cell miRNA. In embodiments, the miRNA-binding sequence is capable of binding an epithelial miRNA.

[0098] In embodiments, the miRNA-binding sequence is capable of hybridizing to a non-endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing toan endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, or a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA. or an epithelial miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a hepatic miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a pancreatic miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a cardiac muscle miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a neural miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a glial miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a skeletal muscle miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a lung miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a cartilage miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a bone miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a vascular smooth muscle miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to an endothelial miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a hematopoietic miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a myeloid miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a pluripotent stem cell miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to an epithelial miRNA.

[0099] In embodiments, the miRNA is anon-endogenous miRNA. In embodiments, the miRNA is an endogenous miRNA. In embodiments, the miRNA is a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA. In embodiments, the miRNA is a hepatic miRNA. In embodiments, the miRNA is a pancreatic miRNA. In embodiments, the miRNA is a cardiac muscle miRNA. In embodiments, the miRNA is a neural miRNA. In embodiments, the miRNA is a glial miRNA. In embodiments, the miRNA is a skeletal muscle miRNA. In embodiments, the miRNA is a lung miRNA. In embodiments, the miRNA is a cartilage miRNA. In embodiments, the miRNA is a bone miRNA. In embodiments, the miRNA is a vascular smooth muscle miRNA. In embodiments, the miRNA is an endothelial miRNA. In embodiments, themiRNA is a hematopoietic miRNA. In embodiments, the miRNA is a myeloid miRNA. In embodiments, the miRNA is a pluripotent stem cell miRNA. In embodiments, the miRNA is an epithelial miRNA.

[0100] In embodiments, the miRNA is miR-192, miR-194, miR-122, miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-17. miR-125, miR-338. miR-128, miR-204, miR-211, miR-203. miR-96, miR-206, miR-145. miR-143, miR-208a, miR-140, miR-199, miR-214, miR-126, miR-451, miR-223, miR-130a, miR-142, miR-181a, miR-191, miR-148a, miR-7, miR-10, miR-125b, miR-132, miR-212, miR-137, miR-184, miR-200, miR-18, miR-21, or miR-302a. In embodiments, the miRNA is miR-192. In embodiments, the miRNA is miR-194. In embodiments, the miRNA is miR-122. In embodiments, the miRNA is miR-375. In embodiments, the miRNA is miR-708, miR-216a. In embodiments, the miRNA is miR-1. In embodiments, the miRNA is miR-133a. In embodiments, the miRNA is miR-124. In embodiments, the miRNA is miR-9. In embodiments, the miRNA is miR-218. In embodiments, the miRNA is miR-219a. In embodiments, the miRNA is miR-216a. In embodiments, the miRNA is miR-133a. In embodiments, the miRNA is miR-17. In embodiments, the miRNA is miR-125. In embodiments, the miRNA is miR-338. In embodiments, the miRNA is miR-128. In embodiments, the miRNA is miR-204. In embodiments, the miRNA is miR-211. In embodiments, the miRNA is miR-203. In embodiments, the miRNA is miR-96. In embodiments, the miRNA is miR-206. In embodiments, the miRNA is miR-145. In embodiments, the miRNA is miR-143. In embodiments, the miRNA is miR-208a. In embodiments, the miRNA is miR-140. In embodiments, the miRNA is miR-199. In embodiments, the miRNA is miR-214. In embodiments, the miRNA is miR-126. In embodiments, the miRNA is miR-451. In embodiments, the miRNA is miR-223. In embodiments, the miRNA is miR-130a. In embodiments, the miRNA is miR-142. In embodiments, the miRNA is miR-181a. In embodiments, the miRNA is miR-191. In embodiments, the miRNA is miR-148a. In embodiments, the miRNA is miR-7. In embodiments, the miRNA is miR-10. In embodiments, the miRNA is miR-125b. In embodiments, the miRNA is miR-132. In embodiments, the miRNA is miR-212. In embodiments, the miRNA is miR-137. In embodiments, the miRNA is miR-184. In embodiments, the miRNA is miR-200. In embodiments, the miRNA is miR-18. In embodiments, the miRNA is miR-21. In embodiments, the miRNA is miR-302a.

[0101] In embodiments, the neural miRNA is miR-9, miR-124, miR-338, miR-128, miR-218, miR-132. miR-212, miR-137, miR-184, miR-125b, or miR-375. In embodiments, the neuralmiRNA is miR-9. In embodiments, the neural miRNA is miR-124. In embodiments, the neural miRNA is miR-338. In embodiments, the neural miRNA is miR-128. In embodiments, the neural miRNA is miR-218. In embodiments, the neural miRNA is miR-132. In embodiments, the neural miRNA is miR-212. In embodiments, the neural miRNA is miR-137. In embodiments, the neural miRNA is miR-184. In embodiments, the neural miRNA is miR-125b. In embodiments, the neural miRNA is miR-375.

[0102] In embodiments, the neural miRNA is a cortical miRNA, a cerebellar miRNA, a motor neuron miRNA, a lens miRNA, a retinal miRNA, a photoreceptor miRNA, or a hippocampal miRNA. In embodiments, the neural miRNA is a cortical miRNA. In embodiments, the cortical miRNA is miR-128. In embodiments, the neural miRNA is a cerebellar miRNA. In embodiments, the cerebellar miRNA is miR-128. In embodiments, the neural miRNA is a motor neuron miRNA. In embodiments, the motor neuron miRNA is miR-218. In embodiments, the neural miRNA is a lens miRNA. In embodiments, the lens miRNA is miR-204. In embodiments, the neural miRNA is a retinal miRNA. In embodiments, the retinal miRNA is miR-204. In embodiments, the neural miRNA is a photoreceptor miRNA. In embodiments, the photoreceptor miRNA is miR-211. In embodiments, the photoreceptor miRNA is a cone miRNA. In embodiments, the cone miRNA is miR-211. In embodiments, the neural miRNA is a hippocampal miRNA. In embodiments, the hippocampal miRNA is miR-137. In embodiments, the hippocampal miRNA is a dentate gyrus miRNA. In embodiments, the dentate gyrus miRNA is miR-137.

[0103] In embodiments, the glial miRNA is an oligodendrocyte miRNA. In embodiments, the glial miRNA is miR-219.

[0104] In embodiments, the skeletal muscle miRNA is miR-206. In embodiments, the cardiac muscle miRNA is miR-143 or miR-208a. In embodiments, the cardiac muscle miRNA is miR-143. In embodiments, the cardiac muscle miRNA is miR-208a. In embodiments, the muscle miRNA is miR-1 or miR-133. In embodiments, the muscle miRNA is miR-1. In embodiments, the muscle miRNA is miR-133. In embodiments, the hepatic miRNA is miR-122 or miR-148a. In embodiments, the hepatic miRNA is miR-122. In embodiments, the hepatic miRNA is miR-148a. In embodiments, the cartilage miRNA is miR-140. In embodiments, the bone miRNA is miR-199 or miR-214. In embodiments, the bone miRNA is miR-199. In embodiments, the bone miRNA is miR-214. In embodiments, the vascular smooth muscle miRNA is miR-145. In embodiments, the endothelial miRNA is miR-126, miR-132, or miR-212. In embodiments, theendothelial miRNA is miR-126. In embodiments, the endothelial miRNA is miR-132. In embodiments, the endothelial miRNA is miR-212.

[0105] In embodiments, the pancreatic miRNA is miR-7 or miR-375. In embodiments, the pancreatic miRNA is miR-7. In embodiments, the pancreatic miRNA is miR-375. In embodiments, the pancreatic miRNA is a pancreatic beta cell miRNA or a pancreatic islets miRNA. In embodiments, the pancreatic miRNA is a pancreatic beta cell miRNA. In embodiments the pancreatic beta cell miRNA is miR-7. In embodiments, the pancreatic miRNA is a pancreatic islets miRNA. In embodiments, the pancreatic islets miRNA is miR-375.

[0106] In embodiments, the miRNA is a pulmonary miRNA, a lung miRNA, a kidney miRNA, an intestinal miRNA. or a splenic miRNA. In embodiments, the miRNA is a pulmonary miRNA. In embodiments, the pulmonary miRNA is miR-10. In embodiments, the miRNA is a lung miRNA. In embodiments, the lung miRNA is miR-10. In embodiments, the miRNA is a kidney miRNA. In embodiments, the kidney miRNA is miR-10. In embodiments, the miRNA is a intestinal miRNA. In embodiments, the intestinal miRNA is miR-10. In embodiments, the miRNA is a splenic miRNA. In embodiments, the splenic miRNA is miR-10.

[0107] In embodiments, the pluripotent stem cell miRNA is miR-21 or miR-302a. In embodiments, the pluripotent stem cell miRNA is miR-21. In embodiments, the pluripotent stem cell miRNA is miR-302a.

[0108] In embodiments, the epithelial miRNA is miR-200, miR-203, miR-137, or miR-184. In embodiments, the epithelial miRNA is miR-200. In embodiments, the epithelial miRNA is miR-203. In embodiments, the epithelial miRNA is miR-137. In embodiments, the epithelial miRNA is miR-184. In embodiments, the epithelial miRNA is a comeal epithelium miRNA. In embodiments, the comeal epithelium miRNA is miR-184. In embodiments, the epithelial miRNA is a colonic epithelium miRNA. In embodiments, the colonic epithelium miRNA is miR-137.

[0109] In embodiments, the hematopoietic miRNA is miR-130a, miR-142, miR-125b, miR-223, miR-181a, or miR-191. In embodiments, the hematopoietic miRNA is miR-130a. In embodiments, the hematopoietic miRNA is miR-142. In embodiments, the hematopoietic miRNA is miR-125b. In embodiments, the hematopoietic miRNA is miR-223. In embodiments, the hematopoietic miRNA is miR-181a. In embodiments, the hematopoietic miRNA is miR-191. In embodiments, the myeloid miRNA is miR-223.

[0110] In embodiments, the miRNA is a sperm miRNA. In embodiments, the sperm miRNA is miR-18.

[0111] In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12. SEQ ID NO: 13, SEQ ID NO: 14. SEQ ID NO: 15, SEQ ID NO: 16. SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75. SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO 78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO 92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97. SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, or SEQ ID NO: 112. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 1. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:2. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:3. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:4. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:5. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 6. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 7. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 8. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 9. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 10. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 11. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 12. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 13. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 14. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 15. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 16. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 73. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:74. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:75. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:76. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:77. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:78. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:79. In embodiments.the miRNA includes the nucleotide sequence of SEQ ID NO: 80. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 81. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 82. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:83. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 84. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:85. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:86. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 87. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 88. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 89. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:90. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:91. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:92. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:93. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:94. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:95. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:96. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 97. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:98. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:99. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 100. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 101. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 102. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 103. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 104. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 105. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 106. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 107. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 108. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 109. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 110. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 111. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 112.

[0112] In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5. SEQ ID NO:6. SEQ ID NO:7. SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO:11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ IDNO: 14. SEQ ID NO: 15, SEQ ID NO: 16. SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75. SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89. SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO 92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97. SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, or SEQ ID NO: 112. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 1. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:2. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:3. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:4. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:5. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:6. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:7. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:8. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:9. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 10. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 11. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 12. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 13. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 14. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 15. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 16. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:73. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:74. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:75. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:76. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:77. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:78. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:79. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 80. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:81. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:82. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:83. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 84. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 85. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:86. In embodiments, the miRNA has the nucleotidesequence of SEQ ID NO:87. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:88. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:89. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:90. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:91. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:92. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:93. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:94. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:95. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:96. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:97. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:98. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:99. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:100. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 101. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 102. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 103. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 104. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 105. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 106. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 107. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 108. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 109. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 110. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 111. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 112

[0113] In embodiments, the miRNA-binding sequence is capable of binding miR-192, miR-194, miR-122, miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-216a, miR-133a, miR-17, miR-125, miR-338, miR-128, miR-204, miR-211, miR-203, miR-96, miR-206, miR-145, miR-143, miR-208a, miR-140, miR-199, miR-214, miR-126, miR-451, miR-223, miR-130a, miR-142, miR-181a, miR-191, miR-148a, miR-7, miR-10, miR-125 b, miR-132, miR-212, miR-137. miR-184, miR-200, miR-18. miR-21, or miR-302a. In embodiments, the miRNA-binding sequence is capable of binding miR-192. In embodiments, the miRNA-binding sequence is capable of binding miR-194. In embodiments, the miRNA-binding sequence is capable of binding miR-122. In embodiments, the miRNA-binding sequence is capable of binding miR-375. In embodiments, the miRNA-binding sequence is capable of binding miR-708. In embodiments, the miRNA-binding sequence is capable ofbinding miR-216a, miR-1. In embodiments, the miRNA-binding sequence is capable of binding miR-133a. In embodiments, the miRNA-binding sequence is capable of binding miR-124. In embodiments, the miRNA-binding sequence is capable of binding miR-9. In embodiments, the miRNA-binding sequence is capable of binding miR-218. In embodiments, the miRNA-binding sequence is capable of binding miR-219a. In embodiments, the miRNA-binding sequence is capable of binding miR-216a. In embodiments, the miRNA-binding sequence is capable of binding miR-133a. In embodiments, the miRNA-binding sequence is capable of binding miR-17. In embodiments, the miRNA-binding sequence is capable of binding miR-125. In embodiments, the miRNA-binding sequence is capable of binding miR-338. In embodiments, the miRNA-binding sequence is capable of binding miR-128. In embodiments, the miRNA-binding sequence is capable of binding miR-204. In embodiments, the miRNA-binding sequence is capable of binding miR-211. In embodiments, the miRNA-binding sequence is capable of binding miR-203. In embodiments, the miRNA-binding sequence is capable of binding miR-96. In embodiments, the miRNA-binding sequence is capable of binding miR-206. In embodiments, the miRNA-binding sequence is capable of binding miR-145. In embodiments, the miRNA-binding sequence is capable of binding miR-143. In embodiments, the miRNA-binding sequence is capable of binding miR-208a. In embodiments, the miRNA-binding sequence is capable of binding miR-140. In embodiments, the miRNA-binding sequence is capable of binding miR-199. In embodiments, the miRNA-binding sequence is capable of binding miR-214. In embodiments, the miRNA-binding sequence is capable of binding miR-126. In embodiments, the miRNA-binding sequence is capable of binding miR-451. In embodiments, the miRNA-binding sequence is capable of binding miR-223. In embodiments, the miRNA-binding sequence is capable of binding miR-130a. In embodiments, the miRNA-binding sequence is capable of binding miR-142. In embodiments, the miRNA-binding sequence is capable of binding miR-181a. In embodiments, the miRNA-binding sequence is capable of binding miR-191. In embodiments, the miRNA-binding sequence is capable of binding miR-148a. In embodiments, the miRNA-binding sequence is capable of binding miR-7, miR-10. In embodiments, the miRNA-binding sequence is capable of binding miR-125b. In embodiments, the miRNA-binding sequence is capable of binding miR-132. In embodiments, the miRNA-binding sequence is capable of binding miR-212. In embodiments, the miRNA-binding sequence is capable of binding miR-137. In embodiments, the miRNA-binding sequence is capable of binding miR-184. In embodiments, the miRNA-binding sequence is capable of binding miR-200. In embodiments, the miRNA-binding sequenceis capable of binding miR-18. In embodiments, the miRNA-binding sequence is capable of binding miR-21. In embodiments, the miRNA-binding sequence is capable of binding miR-302a.

[0114] In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16. SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO 87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92. SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, or SEQ ID NO: 112. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 1. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:2. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:3. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:4. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:5. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:6. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 7. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 8. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:9. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 10. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 11. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 12. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 13. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 14. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 15. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 16. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 73. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:74. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:75. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:76. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 77. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:78. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 79. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 80. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 81. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 82. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:83. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 84. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 85. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 86. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 87. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 88. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 89. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:90. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:91. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:92. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 93. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:94. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:95. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:96. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:97. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:98. In embodiments, the miRNA-binding sequence is capable of binding thenucleotide sequence of SEQ ID NO:99. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 100. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 101. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 102. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 103. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 104. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 105. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 106. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 107. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 108. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 109. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 110. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 111. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 112.

[0115] In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21. SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64. SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO 67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 17. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 18. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 19. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:20. In embodiments, the miRNA-binding domain includes the nucleotide sequenceof SEQ ID NO:21. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:22. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:23. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 24. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 25. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:26. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:27. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 28. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:29. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:30. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:31. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:32. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:33. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:34. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:35. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:36. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 37. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 38. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:39. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 40. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:41. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:42. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:43. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:44. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:45. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:46. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:47. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:48. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:49. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 50. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:51. In embodiments, the miRNA-bindingdomain includes the nucleotide sequence of SEQ ID NO:52. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 53. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 54. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:55. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:56. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:57. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:58. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:59. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:60. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:61. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:62. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 63. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 64. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:65. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 66. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 67. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:68. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:69. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 70. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:71. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:72.

[0116] In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, or SEQ ID NO:32. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 17. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 18. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 19. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 20. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:21. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 22. In embodiments, themiRNA-binding domain has the nucleotide sequence of SEQ ID NO:23. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 24. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:25. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 26. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 27. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 28. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 29. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 30. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:31. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 32. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 33. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 34. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 35. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 36. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 37. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 38. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 39. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 40. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:41. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 42. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:43. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 44. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:45. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 46. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 47. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 48. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 49. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 50. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:51. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 52. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 53. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 54. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 55. In embodiments, themiRNA-binding domain has the nucleotide sequence of SEQ ID NO: 56. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 57. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 58. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 59. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 60. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 61. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 62. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 63. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 64. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 65. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 66. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 67. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 68. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 69. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 70. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 71. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 72.

[0117] In embodiments, the apoptotic domain is a caspase-9 protein, a caspase-3 protein, a caspase-8 protein, a tumor necrosis factor (TNF) protein, a CD95-ligand protein, or a TNF-related apoptosis-inducing ligand (TRAIL) protein. In embodiments, the apoptotic domain is a caspase-9 protein. In embodiments, the apoptotic domain is a caspase-3 protein. In embodiments, the apoptotic domain is a caspase-8 protein. In embodiments, the apoptotic domain is a tumor necrosis factor (TNF) protein. In embodiments, the apoptotic domain is a CD95-ligand protein. In embodiments, the apoptotic domain is a TNF-related apoptosis-inducing ligand (TRAIL) protein.

[0118] In another aspect is provided an isolated nucleic acid including a dimerizing domain, an inducible apoptotic domain, and a lineage-specific binding domain.

[0119] In embodiments, the isolated nucleic acid further includes a reporter domain. In embodiments, the reporter domain encodes a fluorescent reporter.

[0120] In embodiments, the isolated nucleic acid further includes a promoter domain. In embodiments, the isolated nucleic acid further includes a terminator domain. In embodiments, the terminator domain includes a polyA region.

[0121] In embodiments, the dimerizing domain dimerizes in the presences of a chemical dimerizer. In embodiments, the chemical dimerizer is AP20187. In embodiments, the dimerizing of the dimerizing domain activates the apoptotic domain. In embodiments, the activated apoptotic domain induces apoptosis in a cell. In embodiments, the apoptotic domain encodes a Caspase. In embodiments, the Caspase is Caspase9.

[0122] In embodiments, the lineage specific binding domain includes a nucleic acid sequence that is complimentary to a lineage-specific nucleic acid. In embodiments, the lineage-specific nucleic acid is expressed in a lineage-specific cell. In embodiments, the lineage-specific cell is a liver cell, a pancreas cell, a cardiac cell, a neural cell, a glia cell, a muscle cell, or a lung cell.

[0123] In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO: 1. SEQ ID NO:2. SEQ ID NO:3. SEQ ID NO:4. SEQ ID NO:5. SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO: 15, or SEQ ID NO:16. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO:1. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO:2. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO:3. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO:4. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO:5. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO:6. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO:7. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO: 8. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO:9. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO: 10, SEQ ID NO: 11. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO: 12. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO: 13. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO: 14. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO: 15. In embodiments, the lineage specific binding domain includes the nucleic acid sequence of SEQ ID NO: 16.

[0124] In embodiments, the lineage-specific nucleic acid is capable of binding the lineagespecific binding domain.

[0125] In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24. SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO 27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, or SEQ ID NO:32. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO: 17. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO: 18. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO: 19. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:20. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:21. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:22. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO: 23. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO: 24. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:25. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:26. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:27. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:28. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:29. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:30. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:31. In embodiments, the lineage specific nucleic acid includes the nucleic acid sequence of SEQ ID NO:32.

[0126] In embodiments, the lineage-specific nucleic acid is a microRNA (miRNA). In embodiments, the binding of the lineage-specific nucleic acid to the lineage-specific binding domain prevents translation of the apoptotic domain.

[0127] In another aspect is provided an expression vector including the isolated nucleic acid provided herein including embodiments thereof. In another aspect is provided an expression vector including the nucleic acid provided herein including embodiments thereof.CELLULAR COMPOSITIONS

[0128] Provided herein, inter alia, cellular compositions including the nucleic acid provided herein including embodiments thereof. In embodiments, the cellular compositions provided herein include, inter alia, cells and masses of cells (e.g., an organoid or a teratoma) in which each cell includes the nucleic acid compositions provided herein including embodiments thereof. In embodiments, the cellular compositions include recombinant cells. In embodiments, the cellular compositions provided herein may be, inter alia, used in methods of producing masses of cells. In embodiments, the cellular compositions provided herein may be, inter alia, used in methods for sculpting multi-lineage tissues (e.g., teratomas). In embodiments, the cellular compositions are, inter alia, capable of forming masses of cells (e.g., organoids) in vitro or multi-lineage tissues (e.g., teratomas) in vivo. In embodiments, the cellular compositions provided herein may be, inter alia, used to induce apoptosis in a subpopulation of cells in the mass of cells or multi-lineage tissue. In embodiments, the cellular compositions provided herein may be, inter alia, used to prevent apoptosis of a subpopulation of cells in the mass of cells or multi-lineage tissue based on endogenous expression of miRNA in the subpopulation of cells.

[0129] Thus, in an aspect is provided a recombinant cell including the nucleic acid provided herein including embodiments thereof. In embodiments, the recombinant cell is a recombinant pluripotent stem cell.

[0130] In another aspect is provided a mass of recombinant cells, wherein each cell within the mass of recombinant cells includes a nucleic acid including a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein includes a compound-inducible dimerizing domain and an apoptotic domain.

[0131] In embodiments, the mass of recombinant cells includes an acinar cell, an adipogenic mesenchymal stem cell, an adipogenic fibroblast, an airway epithelial cell, a bipolar cell, a chondrocyte, a chondrogenic mesenchymal stem cell, a chondrogenic fibroblast, a choroid plexus cell, a cycling mesenchymal stem cell, a cycling fibroblast, a cycling progenitor cell, a definitive endoderm cell, a differentiating excitatory neuron, a differentiating inhibitory neuron, a dopaminergic neuron, an early differentiating neuron, an early excitatory neuron, an early neuron, an endothelial cell, an enteric neuron, an enterocyte progenitor cell, an ependymal cell, an ependymal precursor cell, an ependymal-like cell, an embryonic stem cell, a foregut epithelial cell, a foveolar cell, a goblet cell, a hematopoietic stem cell, an immune cell, an inhibitoryneuron, an intermediate progenitor cell, a kidney progenitor cell, a lung epithelial progenitor cell, a macrophage, a melanoblast, a melanocyte, a meningeal cell, a midgut epithelial cell, a hindgut epithelial cell, a mesenchymal stem cell, a fibroblast, a muscle progenitor cell, a myofibroblast, a nephron progenitor cell, a neural precursor cell, a neuroblast, a neuroectoderm cell, a neuroendocrine cell, an optic cup cell, a pericyte, a podocyte, a pre-oligodendrocyte progenitor cell, an oligodendrocyte progenitor cell, a radial glia cell, a retinal epithelial cell, a retinal ganglion cell, a retinal interneuron, a retinal neuron, a retinal pigment epithelial cell, a retinal progenitor cell, a radial glia astrocyte cell, an S-shaped body cell, a Schwann cell, a skeletal muscle cell, a cardiac muscle cell, a smooth muscle cell, a suprabasal cell, and / or a trachea basal cell.

[0132] In embodiments, the mass of recombinant cells includes an acinar cell, an adipogenic mesenchymal stem cell, an adipogenic fibroblast, an airway epithelial cell, a bipolar cell, a chondrocyte, a chondrogenic mesenchymal stem cell, a chondrogenic fibroblast, a choroid plexus cell, a cycling mesenchymal stem cell, a cycling fibroblast, a cycling progenitor cell, a definitive endoderm cell, a differentiating excitatory neuron, a differentiating inhibitory neuron, a dopaminergic neuron, an early differentiating neuron, an early excitatory neuron, an early neuron, an endothelial cell, an enteric neuron, an enterocyte progenitor cell, an ependymal cell, an ependymal precursor cell, an ependymal-like cell, an embryonic stem cell, a foregut epithelial cell, a foveolar cell, a goblet cell, a hematopoietic stem cell, an immune cell, an inhibitory neuron, an intermediate progenitor cell, a kidney progenitor cell, a lung epithelial progenitor cell, a macrophage, a melanoblast, a melanocyte, a meningeal cell, a midgut epithelial cell, a hindgut epithelial cell, a mesenchymal stem cell, a fibroblast, a muscle progenitor cell, a myofibroblast, a nephron progenitor cell, a neural precursor cell, a neuroblast, a neuroectoderm cell, a neuroendocrine cell, an optic cup cell, a pericyte, a podocyte, a pre-oligodendrocyte progenitor cell, an oligodendrocyte progenitor cell, a radial glia cell, a retinal epithelial cell, a retinal ganglion cell, a retinal interneuron, a retinal neuron, a retinal pigment epithelial cell, a retinal progenitor cell, a radial glia astrocyte cell, an S-shaped body cell, a Schwann cell, a skeletal muscle cell, a cardiac muscle cell, a smooth muscle cell, a suprabasal cell, or a trachea basal cell.

[0133] In embodiments, the mass of recombinant cells includes an acinar cell. In embodiments, the mass of recombinant cells includes an adipogenic mesenchymal stem cell. In embodiments, the mass of recombinant cells includes an adipogenic fibroblast. In embodiments, the mass of recombinant cells includes an airway epithelial cell. In embodiments, the mass of recombinant cells includes a bipolar cell. In embodiments, the mass of recombinant cellsincludes a chondrocyte. In embodiments, the mass of recombinant cells includes a chondrogenic mesenchymal stem cell. In embodiments, the mass of recombinant cells includes a chondrogenic fibroblast. In embodiments, the mass of recombinant cells includes a choroid plexus cell. In embodiments, the mass of recombinant cells includes a cycling mesenchymal stem cell. In embodiments, the mass of recombinant cells includes a cycling fibroblast. In embodiments, the mass of recombinant cells includes a cycling progenitor cell. In embodiments, the mass of recombinant cells includes a definitive endoderm cell. In embodiments, the mass of recombinant cells includes a differentiating excitatory neuron. In embodiments, the mass of recombinant cells includes a differentiating inhibitory’ neuron. In embodiments, the mass of recombinant cells includes a dopaminergic neuron. In embodiments, the mass of recombinant cells includes an early differentiating neuron. In embodiments, the mass of recombinant cells includes an early excitatory' neuron. In embodiments, the mass of recombinant cells includes an early neuron. In embodiments, the mass of recombinant cells includes an endothelial cell. In embodiments, the mass of recombinant cells includes an enteric neuron. In embodiments, the mass of recombinant cells includes an enterocyte progenitor cell. In embodiments, the mass of recombinant cells includes an ependymal cell. In embodiments, the mass of recombinant cells includes an ependymal precursor cell. In embodiments, the mass of recombinant cells includes an ependymal-like cell. In embodiments, the mass of recombinant cells includes an embryonic stem cell. In embodiments, the mass of recombinant cells includes a foregut epithelial cell. In embodiments, the mass of recombinant cells includes a foveolar cell. In embodiments, the mass of recombinant cells includes a goblet cell. In embodiments, the mass of recombinant cells includes a hematopoietic stem cell. In embodiments, the mass of recombinant cells includes an immune cell. In embodiments, the mass of recombinant cells includes an inhibitory neuron. In embodiments, the mass of recombinant cells includes an intermediate progenitor cell. In embodiments, the mass of recombinant cells includes a kidney progenitor cell. In embodiments, the mass of recombinant cells includes a lung epithelial progenitor cell. In embodiments, the mass of recombinant cells includes a macrophage. In embodiments, the mass of recombinant cells includes a melanoblast. In embodiments, the mass of recombinant cells includes a melanocyte. In embodiments, the mass of recombinant cells includes a meningeal cell. In embodiments, the mass of recombinant cells includes a midgut epithelial cell. In embodiments, the mass of recombinant cells includes a hindgut epithelial cell. In embodiments, the mass of recombinant cells includes a mesenchymal stem cell. In embodiments, the mass of recombinant cells includes a fibroblast. In embodiments, the mass of recombinant cells includes a muscleprogenitor cell. In embodiments, the mass of recombinant cells includes a myofibroblast. In embodiments, the mass of recombinant cells includes a nephron progenitor cell. In embodiments, the mass of recombinant cells includes a neural precursor cell. In embodiments, the mass of recombinant cells includes a neuroblast. In embodiments, the mass of recombinant cells includes a neuroectoderm cell. In embodiments, the mass of recombinant cells includes a neuroendocrine cell. In embodiments, the mass of recombinant cells includes an optic cup cell. In embodiments, the mass of recombinant cells includes a pericyte. In embodiments, the mass of recombinant cells includes a podocyte. In embodiments, the mass of recombinant cells includes a preoligodendrocyte progenitor cell. In embodiments, the mass of recombinant cells includes an oligodendrocyte progenitor cell. In embodiments, the mass of recombinant cells includes a radial glia cell. In embodiments, the mass of recombinant cells includes a retinal epithelial cell. In embodiments, the mass of recombinant cells includes a retinal ganglion cell. In embodiments, the mass of recombinant cells includes a retinal interneuron. In embodiments, the mass of recombinant cells includes a retinal neuron. In embodiments, the mass of recombinant cells includes a retinal pigment epithelial cell. In embodiments, the mass of recombinant cells includes a retinal progenitor cell. In embodiments, the mass of recombinant cells includes a radial glia astrocyte cell. In embodiments, the mass of recombinant cells includes an S-shaped body cell. In embodiments, the mass of recombinant cells includes a Schwann cell. In embodiments, the mass of recombinant cells includes a skeletal muscle cell. In embodiments, the mass of recombinant cells includes a cardiac muscle cell. In embodiments, the mass of recombinant cells includes a smooth muscle cell. In embodiments, the mass of recombinant cells includes a suprabasal cell. In embodiments, the mass of recombinant cells includes a trachea basal cell.

[0134] In embodiments, the nucleic acid includes from 5' to 3', the inducible dimerizing apoptotic protein and the first microRNA (miRNA)-binding sequence.

[0135] In embodiments, the nucleic acid includes a second miRNA-binding sequence. In embodiments, the nucleic acid includes a third miRNA-binding sequence. In embodiments, the nucleic acid includes a fourth miRNA-binding sequence. In embodiments, the nucleic acid further includes a second miRNA-binding sequence, a third miRNA-binding sequence, and a fourth miRNA-binding sequence. In embodiments, the nucleic acid includes a first miRNA-binding sequence, a second miRNA-binding sequence, a third miRNA-binding sequence, and a fourth miRNA-binding sequence.

[0136] In embodiments, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence independently are the same as the first miRNA-binding sequence. In embodiments, the second miRNA-binding sequence is the same as the first miRNA-binding sequence. In embodiments, the third miRNA-binding sequence is the same as the first miRNA-binding sequence. In embodiments, the fourth miRNA-binding sequence is the same as the first miRNA-binding sequence. In embodiments, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence are the same as the first miRNA-binding sequence.

[0137] In embodiments, the nucleic acid includes from 5' to 3', the inducible dimerizing apoptotic protein, the first microRNA (miRNA)-binding sequence, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence.

[0138] In embodiments, the compound is a small molecule compound. In embodiments, the small molecule is a drug compound. In embodiments, the drug compound is AP20187, rimiducid (AP1903), AP21967, rapamycin, gibberellic acid, tamoxifen, lenalidomide, pomalidomide, A1331852, A-1155463, or TMP-POM-7c. In embodiments, the drug compound is AP20187. In embodiments, the drug compound is rimiducid (AP1903). In embodiments, the drug compound is AP21967. In embodiments, the drug compound is rapamycin. In embodiments, the drug compound is gibberellic acid. In embodiments, the drug compound is tamoxifen. In embodiments, the drug compound is lenalidomide. In embodiments, the drug compound is pomalidomide. In embodiments, the drug compound is A1331852. In embodiments, the drug compound is A-1155463. In embodiments, the drug compound is TMP-POM-7c.

[0139] In embodiments, the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain, a FK506-binding protein (FKBP) domain, a FKBP-rapamycin-binding (FRB) domain, a gibberellin-responsive receptor domain, a tamoxifenresponsive estrogen receptor domain, a cereblon-binding domain, a B-cell lymphoma (Bel) interaction domain, or a dihydrofolate reductase domain. In embodiments, the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain. In embodiments, the compound-inducible dimerizing domain is a FK506-binding protein (FKBP) domain. In embodiments, the compound-inducible dimerizing domain is a FKBP-rapamycin-binding (FRB) domain. In embodiments, the compound-inducible dimerizing domain is a gibberellin-responsive receptor domain. In embodiments, the compound-inducible dimerizing domain is a tamoxifen-responsive estrogen receptor domain. In embodiments, the compound-inducible dimerizing domain is a cereblon-binding domain. In embodiments, the compound-inducible dimerizing domain is a B-cell lymphoma (Bel) interaction domain. In embodiments, the compound-inducible dimerizing domain is a dihydrofolate reductase domain.

[0140] In embodiments, the miRNA-binding sequence is capable of binding a non-endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of binding an endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of binding a hepatic miRNA. a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, or a cartilage miRNA a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA. In embodiments, the miRNA-binding sequence is capable of binding a hepatic miRNA. In embodiments, the miRNA-binding sequence is capable of binding a pancreatic miRNA. In embodiments, the miRNA-binding sequence is capable of binding a cardiac muscle miRNA. In embodiments, the miRNA-binding sequence is capable of binding a neural miRNA. In embodiments, the miRNA-binding sequence is capable of binding a glial miRNA. In embodiments, the miRNA-binding sequence is capable of binding a skeletal muscle miRNA. In embodiments, the miRNA-binding sequence is capable of binding a lung miRNA. In embodiments, the miRNA-binding sequence is capable of binding a cartilage miRNA. In embodiments, the miRNA-binding sequence is capable of binding a bone miRNA. In embodiments, the miRNA-binding sequence is capable of binding a vascular smooth muscle miRNA. In embodiments, the miRNA-binding sequence is capable of binding an endothelial miRNA. In embodiments, the miRNA-binding sequence is capable of binding a hematopoietic miRNA. In embodiments, the miRNA-binding sequence is capable of binding a myeloid miRNA. In embodiments, the miRNA-binding sequence is capable of binding a pluripotent stem cell miRNA. In embodiments, the miRNA-binding sequence is capable of binding an epithelial miRNA.

[0141] In embodiments, the miRNA-binding sequence is capable of hybridizing to a non-endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to an endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, or a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a hepatic miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a pancreatic miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a cardiac muscle miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a neural miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a glial miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a skeletal muscle miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a lung miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a cartilage miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a bone miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a vascular smooth muscle miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to an endothelial miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a hematopoietic miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a myeloid miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a pluripotent stem cell miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to an epithelial miRNA.

[0142] In embodiments, the miRNA is anon-endogenous miRNA. In embodiments, the miRNA is an endogenous miRNA. In embodiments, the miRNA is a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, a cartilage miRNA. a bone miRNA, a vascular smooth muscle miRNA. an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA. In embodiments, the miRNA is a hepatic miRNA. In embodiments, the miRNA is a pancreatic miRNA. In embodiments, the miRNA is a cardiac muscle miRNA. In embodiments, the miRNA is a neural miRNA. In embodiments, the miRNA is a glial miRNA. In embodiments, the miRNA is a skeletal muscle miRNA. In embodiments, the miRNA is a lung miRNA. In embodiments, the miRNA is a cartilage miRNA. In embodiments, the miRNA is a bone miRNA. In embodiments, the miRNA is a vascular smooth muscle miRNA. In embodiments, the miRNA is an endothelial miRNA. In embodiments, the miRNA is a hematopoietic miRNA. In embodiments, the miRNA is a myeloid miRNA. In embodiments, the miRNA is a pluripotent stem cell miRNA. In embodiments, the miRNA is an epithelial miRNA.

[0143] In embodiments, the miRNA is miR-192, miR-194, miR-122, miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-17. miR-125, miR-338. miR-128, miR-204, miR-211, miR-203. miR-96, miR-206, miR-145. miR-143,miR-208a, miR-140, miR-199. miR-214, miR-126, miR-451, miR-223. miR-130a, miR-142. miR-181a, miR-191, miR-148a, miR-7, miR-10, miR-125b, miR-132, miR-212, miR-137, miR-184, miR-200, miR-18, miR-21, or miR-302a. In embodiments, the miRNA is miR-192. In embodiments, the miRNA is miR-194. In embodiments, the miRNA is miR-122. In embodiments, the miRNA is miR-375. In embodiments, the miRNA is miR-708, miR-216a. In embodiments, the miRNA is miR-1. In embodiments, the miRNA is miR-133a. In embodiments, the miRNA is miR-124. In embodiments, the miRNA is miR-9. In embodiments, the miRNA is miR-218. In embodiments, the miRNA is miR-219a. In embodiments, the miRNA is miR-216a. In embodiments, the miRNA is miR-133a. In embodiments, the miRNA is miR-17. In embodiments, the miRNA is miR-125. In embodiments, the miRNA is miR-338. In embodiments, the miRNA is miR-128. In embodiments, the miRNA is miR-204. In embodiments, the miRNA is miR-211. In embodiments, the miRNA is miR-203. In embodiments, the miRNA is miR-96. In embodiments, the miRNA is miR-206. In embodiments, the miRNA is miR-145. In embodiments, the miRNA is miR-143. In embodiments, the miRNA is miR-208a. In embodiments, the miRNA is miR-140. In embodiments, the miRNA is miR-199. In embodiments, the miRNA is miR-214. In embodiments, the miRNA is miR-126. In embodiments, the miRNA is miR-451. In embodiments, the miRNA is miR-223. In embodiments, the miRNA is miR-130a. In embodiments, the miRNA is miR-142. In embodiments, the miRNA is miR-181a. In embodiments, the miRNA is miR-191. In embodiments, the miRNA is miR-148a. In embodiments, the miRNA is miR-7. In embodiments, the miRNA is miR-10. In embodiments, the miRNA is miR-125b. In embodiments, the miRNA is miR-132. In embodiments, the miRNA is miR-212. In embodiments, the miRNA is miR-137. In embodiments, the miRNA is miR-184. In embodiments, the miRNA is miR-200. In embodiments, the miRNA is miR-18. In embodiments, the miRNA is miR-21. In embodiments, the miRNA is miR-302a.

[0144] In embodiments, the neural miRNA is miR-9, miR-124, miR-338, miR-128, miR-218, miR-132, miR-212, miR-137, miR-184, miR-125b, or miR-375. In embodiments, the neural miRNA is miR-9. In embodiments, the neural miRNA is miR-124. In embodiments, the neural miRNA is miR-338. In embodiments, the neural miRNA is miR-128. In embodiments, the neural miRNA is miR-218. In embodiments, the neural miRNA is miR-132. In embodiments, the neural miRNA is miR-212. In embodiments, the neural miRNA is miR-137. In embodiments, the neural miRNA is miR-184. In embodiments, the neural miRNA is miR-125b. In embodiments, the neural miRNA is miR-375.

[0145] In embodiments, the neural miRNA is a cortical miRNA, a cerebellar miRNA, a motor neuron miRNA, a lens miRNA, a retinal miRNA, a photoreceptor miRNA, or a hippocampal miRNA. In embodiments, the neural miRNA is a cortical miRNA. In embodiments, the cortical miRNA is miR-128. In embodiments, the neural miRNA is a cerebellar miRNA. In embodiments, the cerebellar miRNA is miR-128. In embodiments, the neural miRNA is a motor neuron miRNA. In embodiments, the motor neuron miRNA is miR-218. In embodiments, the neural miRNA is a lens miRNA. In embodiments, the lens miRNA is miR-204. In embodiments, the neural miRNA is a retinal miRNA. In embodiments, the retinal miRNA is miR-204. In embodiments, the neural miRNA is a photoreceptor miRNA. In embodiments, the photoreceptor miRNA is miR-211. In embodiments, the photoreceptor miRNA is a cone miRNA. In embodiments, the cone miRNA is miR-211. In embodiments, the neural miRNA is a hippocampal miRNA. In embodiments, the hippocampal miRNA is miR-137. In embodiments, the hippocampal miRNA is a dentate gyrus miRNA. In embodiments, the dentate gyrus miRNA is miR-137.

[0146] In embodiments, the glial miRNA is an oligodendrocyte miRNA. In embodiments, the glial miRNA is miR-219.

[0147] In embodiments, the skeletal muscle miRNA is miR-206. In embodiments, the cardiac muscle miRNA is miR-143 or miR-208a. In embodiments, the cardiac muscle miRNA is miR-143. In embodiments, the cardiac muscle miRNA is miR-208a. In embodiments, the muscle miRNA is miR-1 or miR-133. In embodiments, the muscle miRNA is miR-1. In embodiments, the muscle miRNA is miR-133. In embodiments, the hepatic miRNA is miR-122 or miR-148a. In embodiments, the hepatic miRNA is miR-122. In embodiments, the hepatic miRNA is miR-148a. In embodiments, the cartilage miRNA is miR-140. In embodiments, the bone miRNA is miR-199 or miR-214. In embodiments, the bone miRNA is miR-199. In embodiments, the bone miRNA is miR-214. In embodiments, the vascular smooth muscle miRNA is miR-145. In embodiments, the endothelial miRNA is miR-126, miR-132, or miR-212. In embodiments, the endothelial miRNA is miR-126. In embodiments, the endothelial miRNA is miR-132. In embodiments, the endothelial miRNA is miR-212.

[0148] In embodiments, the pancreatic miRNA is miR-7 or miR-375. In embodiments, the pancreatic miRNA is miR-7. In embodiments, the pancreatic miRNA is miR-375. In embodiments, the pancreatic miRNA is a pancreatic beta cell miRNA or a pancreatic islets miRNA. In embodiments, the pancreatic miRNA is a pancreatic beta cell miRNA. Inembodiments the pancreatic beta cell miRNA is miR-7. In embodiments, the pancreatic miRNA is a pancreatic islets miRNA. In embodiments, the pancreatic islets miRNA is miR-375.

[0149] In embodiments, the miRNA is a pulmonary miRNA, a lung miRNA, a kidney miRNA, an intestinal miRNA, or a splenic miRNA. In embodiments, the miRNA is a pulmonary miRNA. In embodiments, the pulmonary miRNA is miR-10. In embodiments, the miRNA is a lung miRNA. In embodiments, the lung miRNA is miR-10. In embodiments, the miRNA is a kidney miRNA. In embodiments, the kidney miRNA is miR-10. In embodiments, the miRNA is a intestinal miRNA. In embodiments, the intestinal miRNA is miR-10. In embodiments, the miRNA is a splenic miRNA. In embodiments, the splenic miRNA is miR-10.

[0150] In embodiments, the pluripotent stem cell miRNA is miR-21 or miR-302a. In embodiments, the pluripotent stem cell miRNA is miR-21. In embodiments, the pluripotent stem cell miRNA is miR-302a.

[0151] In embodiments, the epithelial miRNA is miR-200, miR-203, miR-137, or miR-184. In embodiments, the epithelial miRNA is miR-200. In embodiments, the epithelial miRNA is miR-203. In embodiments, the epithelial miRNA is miR-137. In embodiments, the epithelial miRNA is miR-184. In embodiments, the epithelial miRNA is a comeal epithelium miRNA. In embodiments, the corneal epithelium miRNA is miR-184. In embodiments, the epithelial miRNA is a colonic epithelium miRNA. In embodiments, the colonic epithelium miRNA is miR-137.

[0152] In embodiments, the hematopoietic miRNA is miR-130a, miR-142, miR-125b, miR-223. miR-181a, or miR-191. In embodiments, the hematopoietic miRNA is miR-130a. In embodiments, the hematopoietic miRNA is miR-142. In embodiments, the hematopoietic miRNA is miR-125b. In embodiments, the hematopoietic miRNA is miR-223. In embodiments, the hematopoietic miRNA is miR-181a. In embodiments, the hematopoietic miRNA is miR-191. In embodiments, the myeloid miRNA is miR-223.

[0153] In embodiments, the miRNA is a sperm miRNA. In embodiments, the sperm miRNA is miR-18.

[0154] In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14. SEQ ID NO: 15, SEQ ID NO: 16. SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75. SEQID NO:76, SEQ ID NO:77, SEQ ID NO:78. SEQ ID NO:79, SEQ ID NO:80. SEQ ID NO:81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102. SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, or SEQ ID NO: 112. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 1. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:2. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:3. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:4. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:5. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 6. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:7. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 8. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 9. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 10. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 11. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 12. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 13. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 14. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 15. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 16. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 73. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:74. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:75. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:76. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:77. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:78. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 79. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 80. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 81. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 82. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:83. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 84. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:85. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:86. Inembodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 87. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 88. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 89. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:90. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:91. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:92. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:93. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:94. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:95. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:96. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 97. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:98. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:99. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 100. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 101. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 102. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 103. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 104. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 105. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 106. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 107. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 108. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 109. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 110. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 111. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 112.

[0155] In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14. SEQ ID NO: 15, SEQ ID NO: 16. SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75. SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO 78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO 92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO 95, SEQ ID NO:96, SEQ ID NO:97. SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ IDNO: 104, SEQ ID NO: 105. SEQ ID NO: 106. SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, or SEQ ID NO: 112. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 1. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:2. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:3. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:4. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:5. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:6. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 7. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 8. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 9. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 10. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 11. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 12. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 13. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 14. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 15. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 16. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:73. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 74. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:75. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:76. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:77. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:78. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:79. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 80. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:81. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:82. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:83. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 84. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 85. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 86. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 87. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:88. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:89. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:90. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:91. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:92. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:93. In embodiments, the miRNA has the nucleotide sequence of SEQID NO:94. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:95. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:96. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:97. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:98. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:99. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 100. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 101. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 102. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 103. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 104. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 105. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 106. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 107. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 108. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 109. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 110. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 111. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:112.

[0156] In embodiments, the miRNA-binding sequence is capable of binding miR-192, miR-194, miR-122, miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-216a, miR-133a, miR-17, miR-125. miR-338, miR-128, miR-204, miR-211. miR-203, miR-96, miR-206, miR-145, miR-143, miR-208a, miR-140, miR-199, miR-214, miR-126, miR-451, miR-223, miR-130a, miR-142, miR-181a, miR-191, miR-148a, miR-7, miR-10, miR-125b, miR-132, miR-212, miR-137, miR-184, miR-200, miR-18, miR-21, or miR-302a. In embodiments, the miRNA-binding sequence is capable of binding miR-192. In embodiments, the miRNA-binding sequence is capable of binding miR-194. In embodiments, the miRNA-binding sequence is capable of binding miR-122. In embodiments, the miRNA-binding sequence is capable of binding miR-375. In embodiments, the miRNA-binding sequence is capable of binding miR-708. In embodiments, the miRNA-binding sequence is capable of binding miR-216a, miR-1. In embodiments, the miRNA-binding sequence is capable of binding miR-133a. In embodiments, the miRNA-binding sequence is capable of binding miR-124. In embodiments, the miRNA-binding sequence is capable of binding miR-9. In embodiments, the miRNA-binding sequence is capable of binding miR-218. In embodiments, the miRNA-binding sequence is capable of binding miR-219a. In embodiments, the miRNA-binding sequence is capable of binding miR-216a. In embodiments, the miRNA-binding sequence is capable ofbinding miR-133a. In embodiments, the miRNA-binding sequence is capable of binding miR-17. In embodiments, the miRNA-binding sequence is capable of binding miR-125. In embodiments, the miRNA-binding sequence is capable of binding miR-338. In embodiments, the miRNA-binding sequence is capable of binding miR-128. In embodiments, the miRNA-binding sequence is capable of binding miR-204. In embodiments, the miRNA-binding sequence is capable of binding miR-211. In embodiments, the miRNA-binding sequence is capable of binding miR-203. In embodiments, the miRNA-binding sequence is capable of binding miR-96. In embodiments, the miRNA-binding sequence is capable of binding miR-206. In embodiments, the miRNA-binding sequence is capable of binding miR-145. In embodiments, the miRNA-binding sequence is capable of binding miR-143. In embodiments, the miRNA-binding sequence is capable of binding miR-208a. In embodiments, the miRNA-binding sequence is capable of binding miR-140. In embodiments, the miRNA-binding sequence is capable of binding miR-199. In embodiments, the miRNA-binding sequence is capable of binding miR-214. In embodiments, the miRNA-binding sequence is capable of binding miR-126. In embodiments, the miRNA-binding sequence is capable of binding miR-451. In embodiments, the miRNA-binding sequence is capable of binding miR-223. In embodiments, the miRNA-binding sequence is capable of binding miR-130a. In embodiments, the miRNA-binding sequence is capable of binding miR-142. In embodiments, the miRNA-binding sequence is capable of binding miR-181a. In embodiments, the miRNA-binding sequence is capable of binding miR-191. In embodiments, the miRNA-binding sequence is capable of binding miR-148a. In embodiments, the miRNA-binding sequence is capable of binding miR-7, miR-10. In embodiments, the miRNA-binding sequence is capable of binding miR-125b. In embodiments, the miRNA-binding sequence is capable of binding miR-132. In embodiments, the miRNA-binding sequence is capable of binding miR-212. In embodiments, the miRNA-binding sequence is capable of binding miR-137. In embodiments, the miRNA-binding sequence is capable of binding miR-184. In embodiments, the miRNA-binding sequence is capable of binding miR-200. In embodiments, the miRNA-binding sequence is capable of binding miR-18. In embodiments, the miRNA-binding sequence is capable of binding miR-21. In embodiments, the miRNA-binding sequence is capable of binding miR-302a.

[0157] In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16. SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ IDNO:79. SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84. SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98. SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102. SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106. SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, or SEQ ID NO:112. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 1. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 2. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:3. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:4. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:5. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:6. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 7. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 8. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:9. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 10. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 11. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 12. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 13. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 14. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 15. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 16. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 73. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:74. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:75. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:76. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 77. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence ofSEQ ID NO:78. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:79. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 80. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:81. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 82. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:83. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 84. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:85. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 86. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 87. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 88. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 89. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 90. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:91. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:92. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:93. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:94. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:95. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:96. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 97. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:98. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:99. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 100. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 101. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 102. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 103. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 104. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 105. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 106. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 107. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 108. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 109. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 110. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 111. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 112.

[0158] In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30. SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36. SEQ ID NO:37, SEQ ID NO:38. SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58. SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 17. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 18. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 19. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:20. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:21. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:22. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:23. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:24. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 25. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:26. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:27. In embodiments, themiRNA-binding domain includes the nucleotide sequence of SEQ ID NO:28. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:29. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:30. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:31. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:32. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:33. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 34. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:35. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:36. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 37. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 38. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:39. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 40. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:41. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 42. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:43. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:44. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:45. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:46. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:47. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:48. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:49. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 50. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 51. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:52. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 53. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 54. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 55. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:56. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:57. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQID NO:58. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:59. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 60. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:61. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:62. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 63. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 64. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:65. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 66. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 67. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:68. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:69. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 70. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:71. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:72.

[0159] In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19. SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO 22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27. SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO 42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70. SEQ ID NO:71, or SEQ ID NO:72. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 17. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 18. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 19. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 20. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:21. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 22. In embodiments, themiRNA-binding domain has the nucleotide sequence of SEQ ID NO:23. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 24. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:25. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 26. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 27. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 28. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 29. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 30. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:31. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 32. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 33. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 34. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 35. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 36. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 37. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 38. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 39. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 40. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:41. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 42. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:43. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 44. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:45. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 46. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 47. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 48. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 49. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 50. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:51. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 52. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 53. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 54. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 55. In embodiments, themiRNA-binding domain has the nucleotide sequence of SEQ ID NO: 56. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 57. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 58. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 59. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 60. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 61. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 62. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 63. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 64. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 65. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 66. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 67. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 68. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 69. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 70. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 71. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 72.

[0160] In embodiments, the apoptotic domain is a caspase-9 protein, a caspase-3 protein, a caspase-8 protein, a tumor necrosis factor (TNF) protein, a CD95-ligand protein, or a TNF-related apoptosis-inducing ligand (TRAIL) protein. In embodiments, the apoptotic domain is a caspase-9 protein. In embodiments, the apoptotic domain is a caspase-3 protein. In embodiments, the apoptotic domain is a caspase-8 protein. In embodiments, the apoptotic domain is a tumor necrosis factor (TNF) protein. In embodiments, the apoptotic domain is a CD95-ligand protein. In embodiments, the apoptotic domain is a TNF-related apoptosis-inducing ligand (TRAIL) protein.

[0161] In embodiments, each recombinant cell in the mass of recombinant cells further includes a non-endogenous miRNA. In embodiments, the non-endogenous miRNA is inserted within the genome of each recombinant cell in the mass of recombinant cells. In embodiments, the non-endogenous miRNA is inserted in the genome of each recombinant cell. In embodiments, the non-endogenous miRNA is within a cell-specific gene in the genome of each recombinant cell. In embodiments, the non-endogenous miRNA is inserted in a cell-specific gene in the genome of each recombinant cell. In embodiments, the non-endogenous miRNA is within the 3' UTR of the cell-specific gene. In embodiments, the non-endogenous miRNA isinserted the 3' UTR of the cell-specific gene. In embodiments, the non-endogenous miRNA is expressed under the control of the cell-specific gene.

[0162] In embodiments, the mass of recombinant cells is in vitro.

[0163] In embodiments, the mass of recombinant cells is an organoid or a teratoma. In embodiments, the mass of recombinant cells is an organoid. In embodiments, the mass of recombinant cells is a teratoma.

[0164] In an aspect is provided an organism including the mass of recombinant cells provided herein including embodiments thereof, wherein the organism is a non-human organism.

[0165] In an aspect is provided a cell including the isolated nucleic acid provided herein including embodiments thereof or the expression vector provided herein including embodiments thereof.METHODS OF USE

[0166] The compositions provided herein including embodiments thereof may be, inter alia, used in methods of forming masses of cells (e.g., recombinant cells). In embodiments, the compositions provided herein including embodiments thereof may be, inter alia, used in methods of inducing apoptosis in a portion of cells in a mass of cells. In embodiments, the methods provided herein may be, inter alia, useful for producing masses of recombinant cells, wherein the mass includes different embryonic germ layers (e.g. ectoderm, mesoderm, or endoderm). In embodiments, the method provided herein may be, inter alia, useful for sculpting masses of cells (e.g., organoids) or multi-lineage tissues (e.g., teratomas) to a desired lineage (e.g., neural cells, cartilage cells, etc.). In embodiments, the methods provided herein may be, inter alia, useful for inducing apoptosis in a subpopulation of cells in the mass of cells or multilineage tissue. In embodiments, the methods provided herein may be, inter alia, useful for preventing apoptosis in a desired subpopulation of cells in the mass of cells or multi-lineage tissue based on endogenous expression of miRNA in the desired subpopulation of cells. In embodiments, the methods provided herein including embodiments thereof may be, inter alia, useful for producing cells of a desired developmental or differentiation lineage (e.g., neural cells, cartilage cells, etc.). In embodiments, the cells of the desired developmental or differentiation lineage produced by the methods provided herein may be, inter alia, useful for treating a disease, disorder, or condition in a subject in need thereof.

[0167] Thus, in an aspect is provided a method of forming a mass of recombinant cells, the method includes administering to a subject a plurality of recombinant pluripotent stem cells and allowing the plurality of recombinant pluripotent stem cells to divide for a first period of time, thereby forming the mass of recombinant cells, wherein each recombinant pluripotent stem cell in the plurality of recombinant pluripotent stem cells includes a nucleic acid including a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein includes a compound-inducible dimerizing domain and an apoptotic domain.

[0168] In embodiments, the dividing further includes differentiating the plurality of recombinant pluripotent stem cells within the first period of time. In embodiments, the differentiating the plurality of recombinant pluripotent stem cells includes spontaneous differentiation or directed differentiation. In embodiments, the differentiating the plurality of recombinant pluripotent stem cells includes spontaneous differentiation. In embodiments, the differentiating the plurality of recombinant pluripotent stem cells includes directed differentiation.

[0169] In embodiments, the mass of recombinant cells includes an OCT4-expressing cell, a SOX2-expressing cell, a KLF4-expressing cells, a c-MYC-expressing cell, a PAX6-expressing cell, a GLI3 -expressing cell, a TBR1 -expressing cell, CTIP2-expressing cell, a TMDB15A-expressing cell. aNNAT-expressing cell, a GFAP-expressing cell, an AQP4-expressing cell, an EOMES -expressing cell, a NEURODI -expressing cell, a SATB2-expressing cell, and / or a BRN2-expressing cell. In embodiments, the mass of recombinant cells includes an OCT4-expressing cell, a SOX2-expressing cell, a KLF4-expressing cells, a c-MYC-expressing cell, a PAX6-expressing cell, a GLI3-expressing cell, a TBR1 -expressing cell, CTIP2-expressing cell, a TMDB15A-expressing cell, aNNAT-expressing cell, a GFAP-expressing cell, an AQP4-expressing cell, an EOMES-expressing cell, a NEURODI -expressing cell, a SATB2-expressing cell, or a BRN2-expressing cell. In embodiments, the mass of recombinant cells includes one or more of an OCT4-expressing cell, a SOX2-expressing cell, a KLF4-expressing cells, a c-MYC-expressing cell, a PAX6-expressing cell, a GLI3-expressing cell, a TBR1 -expressing cell, CTlP2-expressing cell, a TMDB15A-expressing cell, a NNAT-expressing cell, a GFAP-expressing cell, an AQP4-expressing cell, an EOMES-expressing cell, a NEURODI -expressing cell, a SATB2-expressing cell, and / or a BRN2-expressing cell. In embodiments, the mass of recombinant cells includes one or more of an OCT4-expressing cell, a SOX2-expressing cell, a KLF4-expressing cells, a c-MYC-expressing cell, a PAX6-expressing cell, a GLI3 -expressingcell, a TBR1 -expressing cell, CTIP2-expressing cell, a TMDB15A-expressing cell, a NNAT-expressing cell, a GF AP -expressing cell, an AQP4-expressing cell, an EOMES -expressing cell, a NEURODI -expressing cell, a SATB2-expressing cell, or a BRN2-expressing cell. In embodiments, the mass of recombinant cells includes an OCT4-expressing cell. In embodiments, the mass of recombinant cells includes a SOX2-expressing cell. In embodiments, the mass of recombinant cells includes a KLF4-expressing cells. In embodiments, the mass of recombinant cells includes a c-MYC-expressing cell. In embodiments, the mass of recombinant cells includes a PAX6-expressing cell. In embodiments, the mass of recombinant cells includes a GLI3-expressing cell. In embodiments, the mass of recombinant cells includes a TBR1 -expressing cell. In embodiments, the mass of recombinant cells includes CTIP2-expressing cell. In embodiments, the mass of recombinant cells includes a TMDB15A-expressing cell. In embodiments, the mass of recombinant cells includes aNNAT-expressing cell. In embodiments, the mass of recombinant cells includes a GFAP-expressing cell. In embodiments, the mass of recombinant cells includes an AQP4-expressing cell. In embodiments, the mass of recombinant cells includes an EOMES-expressing cell. In embodiments, the mass of recombinant cells includes a NEURODI -expressing cell. In embodiments, the mass of recombinant cells includes a SATB2-expressing cell. In embodiments, the mass of recombinant cells includes a BRN2-expressing cell.

[0170] In embodiments, the first period of time is between about 1 week to about 12 weeks. In embodiments, the first period of time is between about 2 weeks to about 12 weeks. In embodiments, the first period of time is between about 3 weeks to about 12 weeks. In embodiments, the first period of time is between about 4 weeks to about 12 weeks. In embodiments, the first period of time is between about 5 weeks to about 12 weeks. In embodiments, the first period of time is between about 6 weeks to about 12 weeks. In embodiments, the first period of time is between about 7 weeks to about 12 weeks. In embodiments, the first period of time is between about 8 weeks to about 12 weeks. In embodiments, the first period of time is between about 9 weeks to about 12 weeks. In embodiments, the first period of time is between about 10 weeks to about 12 weeks. In embodiments, the first period of time is between about 11 weeks to about 12 weeks.

[0171] In embodiments, the first period of time is between about 1 week to about 11 weeks. In embodiments, the first period of time is between about 1 week to about 10 weeks. In embodiments, the first period of time is between about 1 week to about 9 weeks. In embodiments, the first period of time is between about 1 week to about 8 weeks. In embodiments, the first period of time is between about 1 week to about 7 weeks. Inembodiments, the first period of time is between about 1 week to about 6 weeks. In embodiments, the first period of time is between about 1 week to about 5 weeks. In embodiments, the first period of time is between about 1 week to about 4 weeks. In embodiments, the first period of time is between about 1 week to about 3 weeks. In embodiments, the first period of time is between about 1 week to about 2 weeks.

[0172] In embodiments, the first period of time is about 1 week. In embodiments, the first period of time is about 2 weeks. In embodiments, the first period of time is about 3 weeks. In embodiments, the first period of time is about 4 weeks. In embodiments, the first period of time is about 5 weeks. In embodiments, the first period of time is about 6 weeks. In embodiments, the first period of time is about 7 weeks. In embodiments, the first period of time is about 8 weeks. In embodiments, the first period of time is about 9 weeks. In embodiments, the first period of time is about 10 weeks. In embodiments, the first period of time is about 11 weeks. In embodiments, the first period of time is about 12 weeks.

[0173] In embodiments, the method further including isolating the mass of recombinant cells from the subject after the first period of time. In embodiments, the method includes isolating the mass of recombinant cells from the subject after the first period of time.

[0174] In embodiments, the nucleic acid is within the genome of each recombinant pluripotent stem cell. In embodiments, the nucleic acid is inserted in the genome of each recombinant pluripotent stem cell. In embodiments, the nucleic acid is within the adeno-associated virus integration site 1 (AAVS1) locus of the genome of each recombinant pluripotent stem cell. In embodiments, the nucleic acid is inserted in the adeno-associated virus integration site 1 (AAVS1) locus of the genome of each recombinant pluripotent stem cell.

[0175] In embodiments, each recombinant pluripotent stem cell further includes a non-endogenous miRNA. In embodiments, the non-endogenous miRNA is inserted within the genome of each recombinant pluripotent stem cell. In embodiments, the non-endogenous miRNA is inserted in the genome of each recombinant pluripotent stem cell. In embodiments, the non-endogenous miRNA is within a cell-specific gene in the genome of each recombinant pluripotent stem cell. In embodiments, the non-endogenous miRNA is inserted in a cell-specific gene in the genome of each recombinant pluripotent stem cell. In embodiments, the non-endogenous miRNA is within the 3' UTR of the cell-specific gene. In embodiments, the non-endogenous miRNA is inserted the 3' UTR of the cell-specific gene. In embodiments, the non-endogenous miRNA is expressed under the control of the cell-specific gene.

[0176] In embodiments, the mass of recombinant cells is an organoid or a teratoma. In embodiments, the mass of recombinant cells is an organoid. In embodiments, the mass of recombinant cells is a teratoma.

[0177] In another aspect is provided a method for inducing apoptosis in a first portion of recombinant cells in a mass of recombinant cells, the method includes: (a) culturing a mass of recombinant cells in vitro for a first period of time, (b) contacting the mass of recombinant cells with a compound; and (b) culturing the mass of recombinant cells for a second period of time in the presence of the compound, wherein each recombinant stem cell in the mass of recombinant cells includes a nucleic acid including a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein includes a compound-inducible dimerizing domain and an apoptotic domain wherein the mass of recombinant cells includes a first portion of recombinant cells and a second portion of recombinant cells, wherein the second portion of recombinant cells express a miRNA, thereby blocking translation of the inducible dimerizing apoptotic protein, and allowing the second portion of recombinant cells to divide within the second period of time, wherein the first portion of recombinant cells does not express the miRNA, thereby inducing apoptosis in the first portion of recombinant cells in the mass of recombinant cells.

[0178] In embodiments, the culturing of step (a) further includes allowing the mass of recombinant cells to divide within the first period of time. In embodiments, the dividing of step (a) further includes differentiating the mass of recombinant cells within the first period of time.

[0179] In embodiments, the culturing of step (c) further includes allowing the second portion of recombinant cells in the mass of recombinant cells to divide during the second period of time. In embodiments, the dividing of step (c) further includes differentiating the mass of recombinant cells within the first period of time.

[0180] In embodiments, the first period of time is between about 1 week to about 12 months. In embodiments, the first period of time is between about 2 weeks to about 12 months. In embodiments, the first period of time is between about 3 weeks to about 12 months. In embodiments, the first period of time is between about 4 weeks to about 12 months. In embodiments, the first period of time is between about 1 month to about 12 months. In embodiments, the first period of time is between about 2 months to about 12 months. In embodiments, the first period of time is between about 3 months to about 12 months. In embodiments, the first period of time is between about 4 months to about 12 months. Inembodiments, the first period of time is between about 5 months to about 12 months. In embodiments, the first period of time is between about 6 months to about 12 months. In embodiments, the first period of time is between about 7 months to about 12 months. In embodiments, the first period of time is between about 8 months to about 12 months. In embodiments, the first period of time is between about 9 months to about 12 months. In embodiments, the first period of time is between about 10 months to about 12 months. In embodiments, the first period of time is between about 11 months to about 12 months.

[0181] In embodiments, the first period of time is between about 1 week to about 11 months. In embodiments, the first period of time is between about 1 week to about 10 months. In embodiments, the first period of time is between about 1 week to about 9 months. In embodiments, the first period of time is between about 1 week to about 8 months. In embodiments, the first period of time is between about 1 week to about 7 months. In embodiments, the first period of time is between about 1 week to about 6 months. In embodiments, the first period of time is between about 1 week to about 5 months. In embodiments, the first period of time is between about 1 week to about 4 months. In embodiments, the first period of time is between about 1 week to about 3 months. In embodiments, the first period of time is between about 1 week to about 2 months. In embodiments, the first period of time is between about 1 week to about 1 month. In embodiments, the first period of time is between about 1 week to about 4 weeks. In embodiments, the first period of time is between about 1 week to about 3 weeks. In embodiments, the first period of time is between about 1 week to about 2 weeks.

[0182] In embodiments, the first period of time is about 1 week. In embodiments, the first period of time is about 2 weeks. In embodiments, the first period of time is about 3 weeks. In embodiments, the first period of time is about 4 weeks. In embodiments, the first period of time is about 1 month. In embodiments, the first period of time is about 2 months. In embodiments, the first period of time is about 3 months. In embodiments, the first period of time is about 4 months. In embodiments, the first period of time is about 5 months. In embodiments, the first period of time is about 6 months. In embodiments, the first period of time is about 7 months. In embodiments, the first period of time is about 8 months. In embodiments, the first period of time is about 9 months. In embodiments, the first period of time is about 10 months. In embodiments, the first period of time is about 11 months. In embodiments, the first period of time is about 12 months.

[0183] In embodiments, the second period of time is between about 1 week to about 89 months. In embodiments, the second period of time is between about 2 weeks to about 89 months. In embodiments, the second period of time is between about 3 weeks to about 89 months. In embodiments, the second period of time is between about 4 weeks to about 89 months. In embodiments, the second period of time is between about 1 month to about 89 months. In embodiments, the second period of time is between about 2 months to about 89 months. In embodiments, the second period of time is between about 3 months to about 89 months. In embodiments, the second period of time is between about 4 months to about 89 months. In embodiments, the second period of time is between about 5 months to about 89 months. In embodiments, the second period of time is between about 6 months to about 89 months. In embodiments, the second period of time is between about 7 months to about 89 months. In embodiments, the second period of time is between about 8 months to about 89 months. In embodiments, the second period of time is between about 9 months to about 89 months. In embodiments, the second period of time is between about 10 months to about 89 months. In embodiments, the second period of time is between about 11 months to about 89 months. In embodiments, the second period of time is between about 12 months to about 89 months. In embodiments, the second period of time is between about 13 months to about 89 months. In embodiments, the second period of time is between about 14 months to about 89 months. In embodiments, the second period of time is between about 15 months to about 89 months. In embodiments, the second period of time is between about 16 months to about 89 months. In embodiments, the second period of time is between about 17 months to about 89 months. In embodiments, the second period of time is between about 18 months to about 89 months. In embodiments, the second period of time is between about 19 months to about 89 months. In embodiments, the second period of time is between about 20 months to about 89 months. In embodiments, the second period of time is between about 21 months to about 89 months. In embodiments, the second period of time is between about 22 months to about 89 months. In embodiments, the second period of time is between about 23 months to about 89 months. In embodiments, the second period of time is between about 24 months to about 89 months. In embodiments, the second period of time is between about 25 months to about 89 months. In embodiments, the second period of time is between about 26 months to about 89 months. In embodiments, the second period of time is between about 27 months to about 89 months. In embodiments, the second period of time is between about 28 months to about 89 months. In embodiments, the second period of time is between about 29 months to about 89months. In embodiments, the second period of time is between about 30 months to about 89 months. In embodiments, the second period of time is between about 31 months to about 89 months. In embodiments, the second period of time is between about 32 months to about 89 months. In embodiments, the second period of time is between about 33 months to about 89 months. In embodiments, the second period of time is between about 34 months to about 89 months. In embodiments, the second period of time is between about 35 months to about 89 months. In embodiments, the second period of time is between about 36 months to about 89 months. In embodiments, the second period of time is between about 37 months to about 89 months. In embodiments, the second period of time is between about 38 months to about 89 months. In embodiments, the second period of time is between about 39 months to about 89 months.

[0184] In embodiments, the second period of time is between about 40 months to about 89 months. In embodiments, the second period of time is between about 41 months to about 89 months. In embodiments, the second period of time is between about 42 months to about 89 months. In embodiments, the second period of time is between about 43 months to about 89 months. In embodiments, the second period of time is between about 44 months to about 89 months. In embodiments, the second period of time is between about 45 months to about 89 months. In embodiments, the second period of time is between about 46 months to about 89 months. In embodiments, the second period of time is between about 47 months to about 89 months. In embodiments, the second period of time is between about 48 months to about 89 months. In embodiments, the second period of time is between about 49 months to about 89 months. In embodiments, the second period of time is between about 50 months to about 89 months. In embodiments, the second period of time is between about 51 months to about 89 months. In embodiments, the second period of time is between about 52 months to about 89 months. In embodiments, the second period of time is between about 53 months to about 89 months. In embodiments, the second period of time is between about 54 months to about 89 months. In embodiments, the second period of time is between about 55 months to about 89 months. In embodiments, the second period of time is between about 56 months to about 89 months. In embodiments, the second period of time is between about 57 months to about 89 months. In embodiments, the second period of time is between about 58 months to about 89 months. In embodiments, the second period of time is between about 59 months to about 89 months. In embodiments, the second period of time is between about 60 months to about 89 months. In embodiments, the second period of time is between about 61 months to about 89months. In embodiments, the second period of time is between about 62 months to about 89 months. In embodiments, the second period of time is between about 63 months to about 89 months. In embodiments, the second period of time is between about 64 months to about 89 months. In embodiments, the second period of time is between about 65 months to about 89 months. In embodiments, the second period of time is between about 66 months to about 89 months. In embodiments, the second period of time is between about 67 months to about 89 months. In embodiments, the second period of time is between about 68 months to about 89 months. In embodiments, the second period of time is between about 69 months to about 89 months. In embodiments, the second period of time is between about 70 months to about 89 months. In embodiments, the second period of time is between about 71 months to about 89 months. In embodiments, the second period of time is between about 72 months to about 89 months. In embodiments, the second period of time is between about 73 months to about 89 months. In embodiments, the second period of time is between about 74 months to about 89 months. In embodiments, the second period of time is between about 75 months to about 89 months. In embodiments, the second period of time is between about 76 months to about 89 months. In embodiments, the second period of time is between about 77 months to about 89 months. In embodiments, the second period of time is between about 78 months to about 89 months. In embodiments, the second period of time is between about 79 months to about 89 months. In embodiments, the second period of time is between about 80 months to about 89 months. In embodiments, the second period of time is between about 81 months to about 89 months. In embodiments, the second period of time is between about 82 months to about 89 months. In embodiments, the second period of time is between about 83 months to about 89 months. In embodiments, the second period of time is between about 84 months to about 89 months. In embodiments, the second period of time is between about 85 months to about 89 months. In embodiments, the second period of time is between about 86 months to about 89 months. In embodiments, the second period of time is between about 87 months to about 89 months. In embodiments, the second period of time is between about 88 months to about 89 months.

[0185] In embodiments, the second period of time is between about 1 week to about 89 months. In embodiments, the second period of time is between about 1 week to about 88 months. In embodiments, the second period of time is between about 1 week to about 87 months. In embodiments, the second period of time is between about 1 week to about 86 months. In embodiments, the second period of time is between about 1 week to about 85 months. Inembodiments, the second period of time is between about 1 week to about 84 months. In embodiments, the second period of time is between about 1 week to about 83 months. In embodiments, the second period of time is between about 1 week to about 82 months. In embodiments, the second period of time is between about 1 week to about 81 months. In embodiments, the second period of time is between about 1 week to about 80 months. In embodiments, the second period of time is between about 1 week to about 79 months. In embodiments, the second period of time is between about 1 week to about 78 months. In embodiments, the second period of time is between about 1 week to about 77 months. In embodiments, the second period of time is between about 1 week to about 76 months. In embodiments, the second period of time is between about 1 week to about 75 months. In embodiments, the second period of time is between about 1 week to about 74 months. In embodiments, the second period of time is between about 1 week to about 73 months. In embodiments, the second period of time is between about 1 week to about 72 months. In embodiments, the second period of time is between about 1 week to about 71 months. In embodiments, the second period of time is between about 1 week to about 70 months. In embodiments, the second period of time is between about 1 week to about 69 months. In embodiments, the second period of time is between about 1 week to about 68 months. In embodiments, the second period of time is between about 1 week to about 67 months. In embodiments, the second period of time is between about 1 week to about 66 months. In embodiments, the second period of time is between about 1 week to about 65 months. In embodiments, the second period of time is between about 1 week to about 64 months. In embodiments, the second period of time is between about 1 week to about 63 months. In embodiments, the second period of time is between about 1 week to about 62 months. In embodiments, the second period of time is between about 1 week to about 61 months. In embodiments, the second period of time is between about 1 week to about 60 months. In embodiments, the second period of time is between about 1 week to about 59 months. In embodiments, the second period of time is between about 1 week to about 58 months. In embodiments, the second period of time is between about 1 week to about 57 months. In embodiments, the second period of time is between about 1 week to about 56 months. In embodiments, the second period of time is between about 1 week to about 55 months. In embodiments, the second period of time is between about 1 week to about 54 months. In embodiments, the second period of time is between about 1 week to about 53 months. In embodiments, the second period of time is between about 1 week to about 52 months. Inembodiments, the second period of time is between about 1 week to about 51 months. In embodiments, the second period of time is between about 1 week to about 50 months. In embodiments, the second period of time is between about 1 week to about 49 months. In embodiments, the second period of time is between about 1 week to about 48 months. In embodiments, the second period of time is between about 1 week to about 47 months. In embodiments, the second period of time is between about 1 week to about 46 months. In embodiments, the second period of time is between about 1 week to about 45 months. In embodiments, the second period of time is between about 1 week to about 44 months. In embodiments, the second period of time is between about 1 week to about 43 months. In embodiments, the second period of time is between about 1 week to about 42 months. In embodiments, the second period of time is between about 1 week to about 41 months. In embodiments, the second period of time is between about 1 week to about 40 months.

[0186] In embodiments, the second period of time is between about 1 week to about 39 months. In embodiments, the second period of time is between about 1 week to about 38 months. In embodiments, the second period of time is between about 1 week to about 37 months. In embodiments, the second period of time is between about 1 week to about 36 months. In embodiments, the second period of time is between about 1 week to about 35 months. In embodiments, the second period of time is between about 1 week to about 34 months. In embodiments, the second period of time is between about 1 week to about 33 months. In embodiments, the second period of time is between about 1 week to about 32 months. In embodiments, the second period of time is between about 1 week to about 31 months. In embodiments, the second period of time is between about 1 week to about 30 months. In embodiments, the second period of time is between about 1 week to about 29 months. In embodiments, the second period of time is between about 1 week to about 28 months. In embodiments, the second period of time is between about 1 week to about 27 months. In embodiments, the second period of time is between about 1 week to about 26 months. In embodiments, the second period of time is between about 1 week to about 25 months. In embodiments, the second period of time is between about 1 week to about 24 months. In embodiments, the second period of time is between about 1 week to about 23 months. In embodiments, the second period of time is between about 1 week to about 22 months. In embodiments, the second period of time is between about 1 week to about 21 months. In embodiments, the second period of time is between about 1 week to about 20 months. In embodiments, the second period of time is between about 1 week to about 19 months. Inembodiments, the second period of time is between about 1 week to about 18 months. In embodiments, the second period of time is between about 1 week to about 17 months. In embodiments, the second period of time is between about 1 week to about 16 months. In embodiments, the second period of time is between about 1 week to about 15 months. In embodiments, the second period of time is between about 1 week to about 14 months. In embodiments, the second period of time is between about 1 week to about 13 months. In embodiments, the second period of time is between about 1 week to about 12 months. In embodiments, the second period of time is between about 1 week to about 11 months. In embodiments, the second period of time is between about 1 week to about 10 months. In embodiments, the second period of time is between about 1 week to about 9 months. In embodiments, the second period of time is between about 1 week to about 8 months. In embodiments, the second period of time is between about 1 week to about 7 months. In embodiments, the second period of time is between about 1 week to about 6 months. In embodiments, the second period of time is between about 1 week to about 5 months. In embodiments, the second period of time is between about 1 week to about 4 months. In embodiments, the second period of time is between about 1 week to about 3 months. In embodiments, the second period of time is between about 1 week to about 2 months. In embodiments, the second period of time is between about 1 week to about 1 month. In embodiments, the second period of time is between about 1 week to about 4 weeks. In embodiments, the second period of time is between about 1 week to about 3 weeks. In embodiments, the second period of time is between about 1 week to about 2 weeks.

[0187] In embodiments, the second period of time is about 1 week. In embodiments, the second period of time is about 2 weeks. In embodiments, the second period of time is about 3 weeks. In embodiments, the second period of time is about 4 weeks. In embodiments, the second period of time is about 1 month. In embodiments, the second period of time is about 2 months. In embodiments, the second period of time is about 3 months. In embodiments, the second period of time is about 4 months. In embodiments, the second period of time is about 5 months. In embodiments, the second period of time is about 6 months. In embodiments, the second period of time is about 7 months. In embodiments, the second period of time is about 8 months. In embodiments, the second period of time is about 9 months. In embodiments, the second period of time is about 10 months. In embodiments, the second period of time is about 11 months. In embodiments, the second period of time is about 12 months. In embodiments, the second period of time is about 13 months. In embodiments, the second period of time is about 14 months. Inembodiments, the second period of time is about 15 months. In embodiments, the second period of time is about 16 months. In embodiments, the second period of time is about 17 months. In embodiments, the second period of time is about 18 months. In embodiments, the second period of time is about 19 months. In embodiments, the second period of time is about 20 months. In embodiments, the second period of time is about 21 months. In embodiments, the second period of time is about 22 months. In embodiments, the second period of time is about 23 months. In embodiments, the second period of time is about 24 months. In embodiments, the second period of time is about 25 months. In embodiments, the second period of time is about 26 months. In embodiments, the second period of time is about 27 months. In embodiments, the second period of time is about 28 months. In embodiments, the second period of time is about 29 months. In embodiments, the second period of time is about 30 months. In embodiments, the second period of time is about 31 months. In embodiments, the second period of time is about 32 months. In embodiments, the second period of time is about 33 months. In embodiments, the second period of time is about 34 months. In embodiments, the second period of time is about 35 months. In embodiments, the second period of time is about 36 months. In embodiments, the second period of time is about 37 months. In embodiments, the second period of time is about 38 months. In embodiments, the second period of time is about 39 months. In embodiments, the second period of time is about 40 months. In embodiments, the second period of time is about 41 months. In embodiments, the second period of time is about 42 months. In embodiments, the second period of time is about 43 months. In embodiments, the second period of time is about 44 months. In embodiments, the second period of time is about 45 months. In embodiments, the second period of time is about 46 months. In embodiments, the second period of time is about 47 months. In embodiments, the second period of time is about 48 months. In embodiments, the second period of time is about 49 months. In embodiments, the second period of time is about 50 months. In embodiments, the second period of time is about 51 months. In embodiments, the second period of time is about 52 months. In embodiments, the second period of time is about 53 months. In embodiments, the second period of time is about 54 months. In embodiments, the second period of time is about 55 months. In embodiments, the second period of time is about 56 months. In embodiments, the second period of time is about 57 months. In embodiments, the second period of time is about 58 months. In embodiments, the second period of time is about 59 months. In embodiments, the second period of time is about 60 months. In embodiments, the second period of time is about 61 months. In embodiments, the second period of time is about 62 months. In embodiments, the second period of time is about 63 months. In embodiments, the second periodof time is about 64 months. In embodiments, the second period of time is about 65 months. In embodiments, the second period of time is about 66 months. In embodiments, the second period of time is about 67 months. In embodiments, the second period of time is about 68 months. In embodiments, the second period of time is about 69 months. In embodiments, the second period of time is about 70 months. In embodiments, the second period of time is about 71 months. In embodiments, the second period of time is about 72 months. In embodiments, the second period of time is about 73 months. In embodiments, the second period of time is about 74 months. In embodiments, the second period of time is about 75 months. In embodiments, the second period of time is about 76 months. In embodiments, the second period of time is about 77 months. In embodiments, the second period of time is about 78 months. In embodiments, the second period of time is about 79 months. In embodiments, the second period of time is about 80 months. In embodiments, the second period of time is about 81 months. In embodiments, the second period of time is about 82 months. In embodiments, the second period of time is about 83 months. In embodiments, the second period of time is about 84 months. In embodiments, the second period of time is about 85 months. In embodiments, the second period of time is about 86 months. In embodiments, the second period of time is about 87 months. In embodiments, the second period of time is about 88 months. In embodiments, the second period of time is about 89 months.

[0188] In embodiments, the method further includes administering the second portion of recombinant cells of the mass of recombinant cells to a subject in need thereof. In embodiments, the method includes administering the second portion of recombinant cells of the mass of recombinant cells to a subject in need thereof.

[0189] In embodiments, the compound is a small molecule compound. In embodiments, the small molecule is a drug compound. In embodiments, the drug compound is AP20187, rimiducid (AP1903), AP21967. rapamycin. gibberellic acid, tamoxifen, lenalidomide, pomalidomide. A1331852, A-1155463, or TMP-POM-7c. In embodiments, the drug compound is AP20187. In embodiments, the drug compound is rimiducid (AP1903). In embodiments, the drug compound is AP21967. In embodiments, the drug compound is rapamycin. In embodiments, the drug compound is gibberellic acid. In embodiments, the drug compound is tamoxifen. In embodiments, the drug compound is lenalidomide. In embodiments, the drug compound is pomalidomide. In embodiments, the drug compound is A1331852. In embodiments, the drug compound is A-1155463. In embodiments, the drug compound is TMP-POM-7c.

[0190] In embodiments, the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain, a FK506-binding protein (FKBP) domain, a FKBP-rapamycin-binding (FRB) domain, a gibberellin-responsive receptor domain, a tamoxifenresponsive estrogen receptor domain, a cereblon-binding domain, a B-cell lymphoma (Bel) interaction domain, or a dihydrofolate reductase domain. In embodiments, the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain. In embodiments, the compound-inducible dimerizing domain is a FK506-binding protein (FKBP) domain. In embodiments, the compound-inducible dimerizing domain is a FKBP-rapamycin-binding (FRB) domain. In embodiments, the compound-inducible dimerizing domain is a gibberellin-responsive receptor domain. In embodiments, the compound-inducible dimerizing domain is a tamoxifen-responsive estrogen receptor domain. In embodiments, the compound-inducible dimerizing domain is a cereblon-binding domain. In embodiments, the compound-inducible dimerizing domain is a B-cell lymphoma (Bel) interaction domain. In embodiments, the compound-inducible dimerizing domain is a dihydrofolate reductase domain.

[0191] In embodiments, the compound is AP20187 and the compound-inducible dimerizing domain is a DmrB domain. In embodiments, the compound is rimiducid (AP1903) and the compound-inducible dimerizing domain is an FKBP 12 domain. In embodiments, the compound is AP21967 and the compound-inducible dimerizing domain is an FKBP-rapamycin-binding (FRB) domain. In embodiments, the compound is rapamycin and the compound-inducible dimerizing domain is an FKBP-rapamycin-binding (FRB) domain. In embodiments, the compound is gibberellic acid and the compound-inducible dimerizing domain is a Gibberellin Insensitive (GAI) domain or a Gibberellin Insensitive Dwarf 1 (GID1) domain. In embodiments, the compound is tamoxifen and the compound-inducible dimerizing domain is an ERT2 domain. In embodiments, the compound is lenalidomide and the compound-inducible dimerizing domain is a CRBN domain or a CRBN-IZF3 domain. In embodiments, the compound is pomalidomide and the compound-inducible dimerizing domain is a CRBN domain or a CRBN-IZF3 domain. In embodiments, the compound is A1331852 and the compound-inducible dimerizing domain is a B-cell lymphoma (Bel) domain or a pro-apoptotic domain Bim. In embodiments, the compound is A-1155463 and the compound-inducible dimerizing domain is a B-cell lymphoma (Bel) domain or a pro-apoptotic domain Bim. In embodiments, the compound is TMP-POM-7c and the compound-inducible dimerizing domain is a dihydrofolate reductase (DHFR) domain. In embodiments, the FKBP domain includes an FKBP 12 domain or a variant thereof. In embodiments, the FRB domain includes a FKBP-rapamycin-binding domain or a variantthereof. In embodiments, the gibberellin-responsive receptor domain includes a Gibberellin Insensitive (GAI) domain or a Gibberellin Insensitive Dwarf 1 (GID1) domain or a variant thereof. In embodiments, the gibberellin-responsive receptor domain includes a Gibberellin Insensitive (GAI) domain or a variant thereof. In embodiments, the gibberellin-responsive receptor domain includes a Gibberellin Insensitive Dwarf 1 (GID1) domain or a variant thereof. In embodiments, the tamoxifen-responsive estrogen receptor domain includes an ERT2 domain or a variant thereof. In embodiments, the cereblon-binding domain includes a CRBN domain or a CRBN-IZF3 domain or a variant thereof. In embodiments, the cereblon-binding domain includes a CRBN domain or a variant thereof. In embodiments, the cereblon-binding domain includes a CRBN-IZF3 domain or a variant thereof. In embodiments, the B-cell lymphoma (Bel) interaction domain includes a Bcl-XL domain or a pro-apoptotic domain Bim, or variants thereof. In embodiments, the B-cell lymphoma (Bel) interaction domain includes a Bcl-XL domain or variants thereof. In embodiments, the B-cell lymphoma (Bel) interaction domain includes a pro-apoptotic domain Bim or variants thereof. In embodiments, the dihydrofolate reductase domain includes a DHFR domain or a variant thereof.

[0192] In embodiments, the miRNA-binding sequence is capable of binding a non-endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of binding an endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of binding a hepatic miRNA, a pancreatic miRNA. a cardiac muscle miRNA, a neural miRNA, a glial miRNA. a skeletal muscle miRNA, a lung miRNA, or a cartilage miRNA a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA. In embodiments, the miRNA-binding sequence is capable of binding a hepatic miRNA. In embodiments, the miRNA-binding sequence is capable of binding a pancreatic miRNA. In embodiments, the miRNA-binding sequence is capable of binding a cardiac muscle miRNA. In embodiments, the miRNA-binding sequence is capable of binding a neural miRNA. In embodiments, the miRNA-binding sequence is capable of binding a glial miRNA. In embodiments, the miRNA-binding sequence is capable of binding a skeletal muscle miRNA. In embodiments, the miRNA-binding sequence is capable of binding a lung miRNA. In embodiments, the miRNA-binding sequence is capable of binding a cartilage miRNA. In embodiments, the miRNA-binding sequence is capable of binding a bone miRNA. In embodiments, the miRNA-binding sequence is capable of binding a vascular smooth muscle miRNA. In embodiments, the miRNA-binding sequence is capable of binding an endothelial miRNA. In embodiments, the miRNA-binding sequence is capable of binding a hematopoieticmiRNA. In embodiments, the miRNA-binding sequence is capable of binding a myeloid miRNA. In embodiments, the miRNA-binding sequence is capable of binding a pluripotent stem cell miRNA. In embodiments, the miRNA-binding sequence is capable of binding an epithelial miRNA.

[0193] In embodiments, the miRNA-binding sequence is capable of hybridizing to a non-endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to an endogenous miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, or a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a hepatic miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a pancreatic miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a cardiac muscle miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a neural miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a glial miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a skeletal muscle miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a lung miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a cartilage miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a bone miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a vascular smooth muscle miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to an endothelial miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a hematopoietic miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a myeloid miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to a pluripotent stem cell miRNA. In embodiments, the miRNA-binding sequence is capable of hybridizing to an epithelial miRNA.

[0194] In embodiments, the miRNA is anon-endogenous miRNA. In embodiments, the miRNA is an endogenous miRNA. In embodiments, the miRNA is a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA. In embodiments, the miRNA is a hepatic miRNA. Inembodiments, the miRNA is a pancreatic miRNA. In embodiments, the miRNA is a cardiac muscle miRNA. In embodiments, the miRNA is a neural miRNA. In embodiments, the miRNA is a glial miRNA. In embodiments, the miRNA is a skeletal muscle miRNA. In embodiments, the miRNA is a lung miRNA. In embodiments, the miRNA is a cartilage miRNA. In embodiments, the miRNA is a bone miRNA. In embodiments, the miRNA is a vascular smooth muscle miRNA. In embodiments, the miRNA is an endothelial miRNA. In embodiments, the miRNA is a hematopoietic miRNA. In embodiments, the miRNA is a myeloid miRNA. In embodiments, the miRNA is a pluripotent stem cell miRNA. In embodiments, the miRNA is an epithelial miRNA.

[0195] In embodiments, the miRNA is miR-192, miR-194, miR-122, miR-375. miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-17, miR-125, miR-338, miR-128, miR-204, miR-211, miR-203, miR-96, miR-206, miR-145, miR-143, miR-208a, miR-140, miR-199, miR-214, miR-126, miR-451, miR-223, miR-130a, miR-142, miR-181a, miR-191, miR-148a, miR-7, miR-10. miR-125b, miR-132, miR-212, miR-137, miR-184, miR-200, miR-18, miR-21, or miR-302a. In embodiments, the miRNA is miR-192. In embodiments, the miRNA is miR-194. In embodiments, the miRNA is miR-122. In embodiments, the miRNA is miR-375. In embodiments, the miRNA is miR-708, miR-216a. In embodiments, the miRNA is miR-1. In embodiments, the miRNA is miR-133a. In embodiments, the miRNA is miR-124. In embodiments, the miRNA is miR-9. In embodiments, the miRNA is miR-218. In embodiments, the miRNA is miR-219a. In embodiments, the miRNA is miR-216a. In embodiments, the miRNA is miR-133a. In embodiments, the miRNA is miR-17. In embodiments, the miRNA is miR-125. In embodiments, the miRNA is miR-338. In embodiments, the miRNA is miR-128. In embodiments, the miRNA is miR-204. In embodiments, the miRNA is miR-211. In embodiments, the miRNA is miR-203. In embodiments, the miRNA is miR-96. In embodiments, the miRNA is miR-206. In embodiments, the miRNA is miR-145. In embodiments, the miRNA is miR-143. In embodiments, the miRNA is miR-208a. In embodiments, the miRNA is miR-140. In embodiments, the miRNA is miR-199. In embodiments, the miRNA is miR-214. In embodiments, the miRNA is miR-126. In embodiments, the miRNA is miR-451. In embodiments, the miRNA is miR-223. In embodiments, the miRNA is miR-130a. In embodiments, the miRNA is miR-142. In embodiments, the miRNA is miR-181a. In embodiments, the miRNA is miR-191. In embodiments, the miRNA is miR-148a. In embodiments, the miRNA is miR-7. In embodiments, the miRNA is miR-10. In embodiments, the miRNA is miR-125b. In embodiments, the miRNAis miR-132. In embodiments, the miRNA is miR-212. In embodiments, the miRNA is miR-137. In embodiments, the miRNA is miR-184. In embodiments, the miRNA is miR-200. In embodiments, the miRNA is miR-18. In embodiments, the miRNA is miR-21. In embodiments, the miRNA is miR-302a.

[0196] In embodiments, the neural miRNA is miR-9, miR-124, miR-338. miR-128, miR-218, miR-132. miR-212, miR-137, miR-184, miR-125b, or miR-375. In embodiments, the neural miRNA is miR-9. In embodiments, the neural miRNA is miR-124. In embodiments, the neural miRNA is miR-338. In embodiments, the neural miRNA is miR-128. In embodiments, the neural miRNA is miR-218. In embodiments, the neural miRNA is miR-132. In embodiments, the neural miRNA is miR-212. In embodiments, the neural miRNA is miR-137. In embodiments, the neural miRNA is miR-184. In embodiments, the neural miRNA is miR-125b. In embodiments, the neural miRNA is miR-375.

[0197] In embodiments, the neural miRNA is a cortical miRNA, a cerebellar miRNA, a motor neuron miRNA, a lens miRNA, a retinal miRNA, a photoreceptor miRNA, or a hippocampal miRNA. In embodiments, the neural miRNA is a cortical miRNA. In embodiments, the cortical miRNA is miR-128. In embodiments, the neural miRNA is a cerebellar miRNA. In embodiments, the cerebellar miRNA is miR-128. In embodiments, the neural miRNA is a motor neuron miRNA. In embodiments, the motor neuron miRNA is miR-218. In embodiments, the neural miRNA is a lens miRNA. In embodiments, the lens miRNA is miR-204. In embodiments, the neural miRNA is a retinal miRNA. In embodiments, the retinal miRNA is miR-204. In embodiments, the neural miRNA is a photoreceptor miRNA. In embodiments, the photoreceptor miRNA is miR-211. In embodiments, the photoreceptor miRNA is a cone miRNA. In embodiments, the cone miRNA is miR-211. In embodiments, the neural miRNA is a hippocampal miRNA. In embodiments, the hippocampal miRNA is miR-137. In embodiments, the hippocampal miRNA is a dentate gyrus miRNA. In embodiments, the dentate gyrus miRNA is miR-137.

[0198] In embodiments, the glial miRNA is an oligodendrocyte miRNA. In embodiments, the glial miRNA is miR-219.

[0199] In embodiments, the skeletal muscle miRNA is miR-206. In embodiments, the cardiac muscle miRNA is miR-143 or miR-208a. In embodiments, the cardiac muscle miRNA is miR-143. Tn embodiments, the cardiac muscle miRNA is miR-208a. In embodiments, the muscle miRNA is miR-1 or miR-133. In embodiments, the muscle miRNA is miR-1. In embodiments,the muscle miRNA is miR-133. In embodiments, the hepatic miRNA is miR-122 or miR-148a. In embodiments, the hepatic miRNA is miR-122. In embodiments, the hepatic miRNA is miR-148a. In embodiments, the cartilage miRNA is miR-140. In embodiments, the bone miRNA is miR-199 or miR-214. In embodiments, the bone miRNA is miR-199. In embodiments, the bone miRNA is miR-214. In embodiments, the vascular smooth muscle miRNA is miR-145. In embodiments, the endothelial miRNA is miR-126, miR-132, or miR-212. In embodiments, the endothelial miRNA is miR-126. In embodiments, the endothelial miRNA is miR-132. In embodiments, the endothelial miRNA is miR-212.

[0200] In embodiments, the pancreatic miRNA is miR-7 or miR-375. In embodiments, the pancreatic miRNA is miR-7. In embodiments, the pancreatic miRNA is miR-375. In embodiments, the pancreatic miRNA is a pancreatic beta cell miRNA or a pancreatic islets miRNA. In embodiments, the pancreatic miRNA is a pancreatic beta cell miRNA. In embodiments the pancreatic beta cell miRNA is miR-7. In embodiments, the pancreatic miRNA is a pancreatic islets miRNA. In embodiments, the pancreatic islets miRNA is miR-375.

[0201] In embodiments, the miRNA is a pulmonary miRNA, a lung miRNA, a kidney miRNA, an intestinal miRNA, or a splenic miRNA. In embodiments, the miRNA is a pulmonary miRNA. In embodiments, the pulmonary miRNA is miR-10. In embodiments, the miRNA is a lung miRNA. In embodiments, the lung miRNA is miR-10. In embodiments, the miRNA is a kidney miRNA. In embodiments, the kidney miRNA is miR-10. In embodiments, the miRNA is a intestinal miRNA. In embodiments, the intestinal miRNA is miR-10. In embodiments, the miRNA is a splenic miRNA. In embodiments, the splenic miRNA is miR-10.

[0202] In embodiments, the pluripotent stem cell miRNA is miR-21 or miR-302a. In embodiments, the pluripotent stem cell miRNA is miR-21. In embodiments, the pluripotent stem cell miRNA is miR-302a.

[0203] In embodiments, the epithelial miRNA is miR-200, miR-203, miR-137, or miR-184. In embodiments, the epithelial miRNA is miR-200. In embodiments, the epithelial miRNA is miR-203. In embodiments, the epithelial miRNA is miR-137. In embodiments, the epithelial miRNA is miR-184. In embodiments, the epithelial miRNA is a comeal epithelium miRNA. In embodiments, the comeal epithelium miRNA is miR-184. In embodiments, the epithelial miRNA is a colonic epithelium miRNA. In embodiments, the colonic epithelium miRNA is miR-137.

[0204] In embodiments, the hematopoietic miRNA is miR-130a, miR-142, miR-125b, miR-223, miR-181a, or miR-191. In embodiments, the hematopoietic miRNA is miR-130a. In embodiments, the hematopoietic miRNA is miR-142. In embodiments, the hematopoietic miRNA is miR-125b. In embodiments, the hematopoietic miRNA is miR-223. In embodiments, the hematopoietic miRNA is miR-181a. In embodiments, the hematopoietic miRNA is miR-191. In embodiments, the myeloid miRNA is miR-223.

[0205] In embodiments, the miRNA is a sperm miRNA. In embodiments, the sperm miRNA is miR-18.

[0206] In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12. SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO 75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85. SEQ ID NO: 86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89. SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO:103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO:107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111. or SEQ ID NO: 112. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 1. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:2. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:3. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:4. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:5. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 6. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:7. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 8. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 9. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 10. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 11. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 12. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 13. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 14. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 15. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 16. In embodiments, the miRNAincludes the nucleotide sequence of SEQ ID NO:73. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:74. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:75. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:76. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:77. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:78. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:79. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 80. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 81. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 82. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:83. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 84. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:85. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:86. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 87. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 88. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 89. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:90. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:91. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:92. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:93. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:94. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:95. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:96. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 97. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:98. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO:99. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 100. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 101. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 102. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 103. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 104. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 105. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 106. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 107. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 108. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 109. Inembodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 110. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 111. In embodiments, the miRNA includes the nucleotide sequence of SEQ ID NO: 112.

[0207] In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5. SEQ ID NO:6. SEQ ID NO:7. SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO:11, SEQ ID NO: 12. SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO 75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO:87. SEQ ID NO:88, SEQ ID NO:89. SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO:103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO:107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111. or SEQ ID NO: 112. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 1. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:2. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:3. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:4. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:5. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:6. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:7. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 8. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 9. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 10. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 11. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 12. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 13. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:14. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:15. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 16. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 73. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:74. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:75. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:76. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:77. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 78. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:79. In embodiments, the miRNA has thenucleotide sequence of SEQ ID NO: 80. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:81. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:82. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:83. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 84. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 85. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 86. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 87. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:88. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:89. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:90. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:91. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:92. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:93. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:94. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:95. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:96. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:97. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:98. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO:99. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 100. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 101. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 102. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 103. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 104. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 105. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 106. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 107. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 108. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 109. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 110. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 111. In embodiments, the miRNA has the nucleotide sequence of SEQ ID NO: 112.

[0208] In embodiments, the miRNA-binding sequence is capable of binding miR-192, miR-194, miR-122, miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-216a, miR-133a, miR-17, miR-125, miR-338, miR-128, miR-204, miR-211, miR-203. miR-96, miR-206, miR-145. miR-143, miR-208a. miR-140, miR-199, miR-214, miR-126, miR-451, miR-223, miR-130a, miR-142, miR-181a, miR-191, miR-148a, miR-7,miR-10, miR-125 b, miR-132, miR-212, miR-137. miR-184, miR-200, miR-18. miR-21, or miR-302a. In embodiments, the miRNA-binding sequence is capable of binding miR-192. In embodiments, the miRNA-binding sequence is capable of binding miR-194. In embodiments, the miRNA-binding sequence is capable of binding miR-122. In embodiments, the miRNA-binding sequence is capable of binding miR-375. In embodiments, the miRNA-binding sequence is capable of binding miR-708. In embodiments, the miRNA-binding sequence is capable of binding miR-216a, miR-1. In embodiments, the miRNA-binding sequence is capable of binding miR-133a. In embodiments, the miRNA-binding sequence is capable of binding miR-124. In embodiments, the miRNA-binding sequence is capable of binding miR-9. In embodiments, the miRNA-binding sequence is capable of binding miR-218. In embodiments, the miRNA-binding sequence is capable of binding miR-219a. In embodiments, the miRNA-binding sequence is capable of binding miR-216a. In embodiments, the miRNA-binding sequence is capable of binding miR-133a. In embodiments, the miRNA-binding sequence is capable of binding miR-17. In embodiments, the miRNA-binding sequence is capable of binding miR-125. In embodiments, the miRNA-binding sequence is capable of binding miR-338. In embodiments, the miRNA-binding sequence is capable of binding miR-128. In embodiments, the miRNA-binding sequence is capable of binding miR-204. In embodiments, the miRNA-binding sequence is capable of binding miR-211. In embodiments, the miRNA-binding sequence is capable of binding miR-203. In embodiments, the miRNA-binding sequence is capable of binding miR-96. In embodiments, the miRNA-binding sequence is capable of binding miR-206. In embodiments, the miRNA-binding sequence is capable of binding miR-145. In embodiments, the miRNA-binding sequence is capable of binding miR-143. In embodiments, the miRNA-binding sequence is capable of binding miR-208a. In embodiments, the miRNA-binding sequence is capable of binding miR-140. In embodiments, the miRNA-binding sequence is capable of binding miR-199. In embodiments, the miRNA-binding sequence is capable of binding miR-214. In embodiments, the miRNA-binding sequence is capable of binding miR-126. In embodiments, the miRNA-binding sequence is capable of binding miR-451. In embodiments, the miRNA-binding sequence is capable of binding miR-223. In embodiments, the miRNA-binding sequence is capable of binding miR-130a. In embodiments, the miRNA-binding sequence is capable of binding miR-142. In embodiments, the miRNA-binding sequence is capable of binding miR-181a. In embodiments, the miRNA-binding sequence is capable of binding miR-191. In embodiments, the miRNA-binding sequence is capable of binding miR-148a. In embodiments, the miRNA-binding sequence is capable of binding miR-7, miR-10. In embodiments, the miRNA-binding sequence iscapable of binding miR-125b. In embodiments, the miRNA-binding sequence is capable of binding miR-132. In embodiments, the miRNA-binding sequence is capable of binding miR-212. In embodiments, the miRNA-binding sequence is capable of binding miR-137. In embodiments, the miRNA-binding sequence is capable of binding miR-184. In embodiments, the miRNA-binding sequence is capable of binding miR-200. In embodiments, the miRNA-binding sequence is capable of binding miR-18. In embodiments, the miRNA-binding sequence is capable of binding miR-21. In embodiments, the miRNA-binding sequence is capable of binding miR-302a.

[0209] In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:1. SEQ ID NO:2. SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6. SEQ ID NO:7. SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO: 10, SEQ ID NO: 11. SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO 84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO 87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92. SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, or SEQ ID NO: 112. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 1. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:2. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:3. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:4. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:5. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:6. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 7. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 8. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:9. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 10. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 11. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 12. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 13. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 14. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 15. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 16. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:73. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:74. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:75. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:76. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 77. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 78. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:79. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 80. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:81. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 82. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:83. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 84. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 85. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 86. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:87. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 88. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 89. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:90. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:91. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:92. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:93. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:94. In embodiments, the miRNA-binding sequence is capable of binding thenucleotide sequence of SEQ ID NO:95. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:96. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 97. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:98. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO:99. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 100. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 101. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 102. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 103. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 104. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 105. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 106. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 107. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 108. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 109. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 110. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 111. In embodiments, the miRNA-binding sequence is capable of binding the nucleotide sequence of SEQ ID NO: 112.

[0210] In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41. SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO 50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64. SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO 67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72. Inembodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 17. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 18. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 19. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:20. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:21. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:22. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:23. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 24. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 25. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:26. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:27. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 28. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:29. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:30. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:31. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:32. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 33. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 34. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:35. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:36. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 37. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 38. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:39. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 40. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:41. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:42. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:43. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:44. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:45. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:46. In embodiments, the miRNA-binding domain includes the nucleotide sequenceof SEQ ID NO:47. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:48. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:49. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 50. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:51. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:52. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 53. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 54. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:55. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:56. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:57. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:58. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:59. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:60. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:61. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:62. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 63. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 64. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:65. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 66. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 67. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:68. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:69. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 70. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:71. In embodiments, the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:72.

[0211] In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO 25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQID NO:39, SEQ ID NO:40, SEQ ID NO:41. SEQ ID NO:42, SEQ ID NO:43. SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO 58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63. SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 17. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 18. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 19. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:20. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:21. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 22. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO 23. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 24. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 25. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:26. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:27. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:28. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:29. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 30. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:31. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:32. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 33. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:34. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:35. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 36. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:37. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:38. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 39. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 40. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:41. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 42. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 43. Inembodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:44. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:45. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:46. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:47. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:48. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:49. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:50. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:51. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:52. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:53. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:54. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO: 55. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:56. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:57. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:58. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:59. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:60. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:61. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:62. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:63. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:64. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:65. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:66. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:67. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:68. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:69. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:70. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:71. In embodiments, the miRNA-binding domain has the nucleotide sequence of SEQ ID NO:72.

[0212] In embodiments, the apoptotic domain is a caspase-9 protein, a caspase-3 protein, a caspase-8 protein, a tumor necrosis factor (TNF) protein, a CD95-ligand domain, or a TNF-related apoptosis-inducing ligand (TRAIL) protein. In embodiments, the apoptotic domain is a caspase-9 protein. In embodiments, the apoptotic domain is a caspase-3 protein. In embodiments,the apoptotic domain is a caspase-8 protein. In embodiments, the apoptotic domain is a tumor necrosis factor (TNF) protein. In embodiments, the apoptotic domain is a CD95-ligand protein. In embodiments, the apoptotic domain is a TNF-related apoptosis-inducing ligand (TRAIL) protein.

[0213] In another aspect is provided a method for generating a multi-lineage population of cells, the method including: (a) contacting a population of cells with one or more of the isolated nucleic acids provided herein including embodiments thereof or the expression vector provided herein including embodiments thereof; (b) allow the cells to express the one or more isolated nucleic acids: and (c) contacting the population of cells with a chemical dimerizer, wherein the chemical dimerizer induces the dimerization of one or more dimerizing domains.

[0214] In embodiments, the chemical dimerizer is AP20187. In embodiments, the dimerizing of the dimerizing domain activates the one or more apoptotic domains. In embodiments, the one or more activated apoptotic domains induces apoptosis in a cell. In embodiments, the one or more apoptotic domains encodes a Caspase. In embodiments, the Caspase is Caspase9.

[0215] In embodiments, the one or more lineage specific binding domains include a nucleic acid sequence that is complimentary to one or more lineage-specific nucleic acids. In embodiments, the one or more lineage-specific nucleic acids are expressed in a lineage-specific cell. In embodiments, the lineage-specific cell is a liver cell, a pancreas cell, a cardiac cell, a neural cell, a glia cell, a muscle cell, or a lung cell.

[0216] In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, or SEQ ID NO: 16. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 1. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO:2. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO:3. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO:4. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO:5. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 6. Inembodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO:7. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 8. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO:9. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 10, SEQ ID NO: 11. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 12. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 13. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 14. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 15. In embodiments, the one or more lineage specific binding domains independently include the nucleic acid sequence of SEQ ID NO: 16.

[0217] In embodiments, the one or more lineage-specific nucleic acids are capable of binding the one or more lineage-specific binding domains.

[0218] In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28. SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31. or SEQ ID NO:32. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO: 17. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO: 18. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO: 19. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:20. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:21. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:22. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:23. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:24. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:25. In embodiments, the one ormore lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO: 26. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:27. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:28. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:29. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO: 30. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO:31. In embodiments, the one or more lineage specific nucleic acids independently include the nucleic acid sequence of SEQ ID NO: 32.

[0219] In embodiments, the lineage-specific nucleic acid is a microRNA (miRNA). In embodiments, the binding of the lineage-specific nucleic acid to the lineage-specific binding domain prevents translation of the apoptotic domain.

[0220] In embodiments, the one or more lineage-specific nucleic acids are one or more microRNAs (miRNAs). In embodiments, the binding of the one or more lineage-specific nucleic acids to the one or more lineage-specific binding domain prevents translation of the one or more apoptotic domain.

[0221] In embodiments, the method further includes: (d) contacting the cells with one or more differentiation agents.EXAMPLESExample 1

[0222] The invention described here makes use of microRNA (miRNA)-mediated suicide gene circuits, to molecularly sculpt organ tissue in multi-lineage environments such as the teratoma. This is achieved by employing a microRNA-guided suicide gene circuit, enabling the enrichment of desired cell types and simultaneous depletion of undesired ones. As described below, this approach leverages a suicide gene circuit composed of a drug-inducible Caspase9 (iCaspase9), flanked by lineage-specific microRNA (miRNA) target site in the 3’ UTR of the transgene. In the absence of the drug AP20187, iCaspase9 molecules remain as inactive homodimers; however, upon addition of AP20187, iCaspase9 molecules dimerize and trigger apoptosis. The inclusion of the miRNA target site flanking the transgene allows for cell-type level control of the genetic sw itch, as endogenous expression of a lineage-specific miRNA will silence the iCaspase9 transcript, and prevent apoptosis in desired cells, ultimately enabling cell-type specificenrichment in a multi-lineage tissue environment. Here, we integrate this miRNA-mediated genetic circuit into the AAVS1 genetic safe harbor locus of human pluripotent stem cells (hPSCs) and generate teratomas via the subcutaneous injection hPSCs into immunodeficient NOD. Cg-Prkdc scid I12rg tmlWjl / SzJ (NSG) mice. During teratoma growth, tissue sculpting is conducted by administering the chemical dimerizer AP20187 via intraperitoneal and intratumoral injections. This compound induces apoptosis in undesired cell types, leading to the enrichment and maturation of desired cell types within a vascularized, in vivo scaffold.Example 2: General Methods for Teratoma Generation

[0223] The teratoma is currently the gold-standard assay for hPSC pluripotency and is formed by subcutaneous injection of a 1:1 mixture of hPSCs and Matrigel in immunodeficient mice 16. The resulting tumor is a large (~3 cm after 8 weeks of growth) mass of vascularized human tissue that contains cell-types from all three germ layers. The teratoma is very easy to grow and contains many complex and self-organized tissue structures that all arise spontaneously. This qualifies the teratoma as a unique and powerful launching pad for organ engineering.

[0224] Teratomas form from random differentiation of hPSCs to an assortment of cell-types; thus, to successfully use the teratoma for organ engineering, we need a way to sculpt the tissue towards a particular lineage. MicroRNAs (miRNAs) are small non-coding RNAs that are typically 20-26 nucleotides in length 17. They act post-transcriptionally, targeting specific messenger RNAs (mRNAs) in a sequence-specific manner 18. miRNAs have extensively been studied as powerful developmental regulators, and they typically act in feed-back or feedforward loops, rein...

Claims

PATENT Attorney Docket No.: 048537-663001 WO WHAT IS CLAIMED IS:

1. A nucleic acid comprising a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein comprises a compound-inducible dimerizing domain and an apoptotic domain.

2. The nucleic acid of claim 1, wherein the nucleic acid comprises from 5' to 3', the inducible dimerizing apoptotic protein and the first microRNA (miRNA)-binding sequence.

3. The nucleic acid of claim 1, further comprising a second miRNA-binding sequence, a third miRNA-binding sequence, and a fourth miRNA-binding sequence.

4. The nucleic acid of claim 3, wherein the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence are the same as the first miRNA-binding sequence.

5. The nucleic acid of claim 3, wherein the nucleic acid comprises from 5' to 3', the inducible dimerizing apoptotic protein, the first microRNA (miRNA)-binding sequence, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence.

6. The nucleic acid of claim 1, wherein the compound is a small molecule compound.

7. The nucleic acid of claim 6, wherein the small molecule is a drug compound.

8. The nucleic acid of claim 7, wherein the drug compound is AP20187, rimiducid (AP1903), AP21967, rapamycin, gibberellic acid, tamoxifen, lenalidomide, pomalidomide. A1331852. A-1155463, or TMP-POM-7c.

9. The nucleic acid of claim 1, wherein the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain, a FK506-binding protein (FKBP) domain, a FKBP-rapamycin-binding (FRB) domain, a gibberellin-responsive receptor domain, a tamoxifen-responsive estrogen receptor domain, a cereblon-binding domain, a B-cell lymphoma (Bcl) interaction domain, or a dihydrofolate reductase domain.PATENT Attorney Docket No.: 048537-663001 WO10. The nucleic acid of claim 1, wherein the miRNA-binding sequence is capable of binding a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA. a skeletal muscle miRNA, a lung miRNA. a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA.

11. The nucleic acid of claim 1, wherein the miRNA-binding sequence is capable of binding miR-192, miR-194, miR-122, miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-216a, miR-133a, miR-17, miR-125, miR-338, miR-128, miR-204, miR-211, miR-203, miR-96, miR-206, miR-145, miR-143, miR-208a, miR-140, miR-199, miR-214, miR-126, miR-451. miR-223, miR-130a, miR-142, miR-181a, miR-191, miR-148a, miR-7, miR-10, miR-125b, miR-132, miR-212, miR-137, miR-184, miR-200, miR-18, miR-21, or miR-302a.

12. The nucleic acid of claim 1, wherein the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:

39. SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:

42. SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:

56. SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:

60. SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:

65. SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72.

13. The nucleic acid of claim 1, wherein the apoptotic domain is a caspase-9 protein, a caspase-3 protein, a caspase-8 protein, a tumor necrosis factor (TNF) protein, a CD95-ligand protein, or a TNF-related apoptosis-inducing ligand (TRAIL) protein.

14. A recombinant cell comprising the nucleic acid of claim 1.

15. The recombinant cell of claim 14, wherein the cell is a recombinant pluripotent stem cell.PATENT Attorney Docket No.: 048537-663001 WO16. A mass of recombinant cells, wherein each cell within the mass of recombinant cells comprises a nucleic acid comprising a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein comprises a compound-inducible dimerizing domain and an apoptotic domain.

17. The mass of recombinant cells of claim 16, wherein the nucleic acid comprises from 5' to 3', the inducible dimerizing apoptotic protein and the first microRNA (miRNA)-binding sequence.

18. The mass of recombinant cells of claim 16, further comprising a second miRNA-binding sequence, a third miRNA-binding sequence, and a fourth miRNA-binding sequence.

19. The mass of recombinant cells of claim 18, wherein the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence are the same as the first miRNA-binding sequence.

20. The mass of recombinant cells of claim 18, wherein the nucleic acid comprises from 5' to 3', the inducible dimerizing apoptotic protein, the first microRNA (miRNA)-binding sequence, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence.

21. The mass of recombinant cells of claim 16, wherein the compound is a small molecule compound.

22. The mass of recombinant cells of claim 21, wherein the small molecule is a drug compound.

23. The mass of recombinant cells of claim 22, wherein the drug compound is AP20187, rimiducid (AP1903), AP21967. rapamycin. gibberellic acid, tamoxifen, lenalidomide, pomalidomide, A1331852, A-1155463, or TMP-POM-7c.

24. The mass of recombinant cells of claim 16, wherein the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain, a FK506-binding protein (FKBP) domain, a FKBP-rapamycin-binding (FRB) domain, a gibberellin-responsive receptor domain, a tamoxifen-responsive estrogen receptor domain, aPATENT Attorney Docket No.: 048537-663001 WO cereblon-binding domain, a B-cell lymphoma (Bel) interaction domain, or a dihydrofolate reductase domain.

25. The mass of recombinant cells of claim 16, wherein the miRNA is a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA.

26. The mass of recombinant cells of claim 16, wherein the miRNA is miR-192, miR-194, miR-122, miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a. miR-216a, miR-133a, miR-17, miR-125, miR-338, miR-128, miR-204, miR-211, miR-203, miR-96, miR-206, miR-145, miR-143, miR-208a, miR-140, miR-199, miR-214, miR-126, miR-451, miR-223, miR-130a, miR-142, miR-181a, miR-191, miR-148a, miR-7, miR-10, miR-125b, miR-132, miR-212, miR-137, miR-184, miR-200, miR-18, miR-21, or miR-302a.

27. The mass of recombinant cells of claim 16, wherein the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:

21. SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:

25. SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:

28. SEQ ID NO:29, SEQ ID NO:

30. SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:

47. SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:

50. SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72.

28. The mass of recombinant cells of claim 16, wherein the apoptotic domain is a caspase-9 protein, a caspase-3 protein, a caspase-8 protein, a tumor necrosis factor (TNF) protein, a CD95-ligand protein, or a TNF-related apoptosis-inducing ligand (TRAIL) protein.

29. The mass of recombinant cells of claim 16, wherein the mass of recombinant cells is in vitro.PATENT Attorney Docket No.: 048537-663001 WO30. The mass of recombinant cells of claim 16, wherein the mass of recombinant cells is an organoid or a teratoma.

31. An organism comprising the mass of recombinant cells of claim 16, wherein the organism is a non-human organism.

32. A method of forming a mass of recombinant cells, the method comprising administering to a subject a plurality of recombinant pluripotent stem cells and allowing the plurality of recombinant pluripotent stem cells to divide for a first period of time, thereby forming the mass of recombinant cells, wherein each recombinant pluripotent stem cell in the plurality of recombinant pluripotent stem cells comprises a nucleic acid comprising a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein comprises a compound-inducible dimerizing domain and an apoptotic domain.

33. The method of claim 32, wherein the nucleic acid comprises from 5' to 3', the inducible dimerizing apoptotic protein and the first microRNA (miRNA)-binding sequence.

34. The method of claim 32, further comprising a second miRNA-binding sequence, a third miRNA-binding sequence, and a fourth miRNA-binding sequence.

35. The method of claim 34, wherein the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence are the same as the first miRNA-binding sequence.

36. The method of claim 48, wherein the nucleic acid comprises from 5' to 3', the inducible dimerizing apoptotic protein, the first microRNA (miRNA)-binding sequence, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence.

37. The method of claim 32, wherein the compound is a small molecule compound.

38. The method of claim 37, wherein the small molecule is a drug compound.PATENT Attorney Docket No.: 048537-663001 WO39. The method of claim 38, wherein the drug compound is AP20187, rimiducid (AP1903), AP21967, rapamycin, gibberellic acid, tamoxifen, lenalidomide, pomalidomide. A1331852. A-1155463, or TMP-POM-7c.

40. The method of claim 32, wherein the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain, a FK506-binding protein (FKBP) domain, a FKBP-rapamycin-binding (FRB) domain, a gibberellin-responsive receptor domain, a tamoxifen-responsive estrogen receptor domain, a cerebl on-binding domain, a B-cell lymphoma (Bel) interaction domain, or a dihydrofolate reductase domain.

41. The method of claim 32, wherein the miRNA is a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletal muscle miRNA, a lung miRNA, a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA.

42. The method of claim 32, wherein the miRNA is miR-192, miR-194, miR-122, miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-216a, miR-133a, miR-17, miR-125, miR-338, miR-128, miR-204. miR-211, miR-203, miR-96, miR-206, miR-145, miR-143, miR-208a, miR-140, miR-199, miR-214, miR-126, miR-451, miR-223, miR-130a, miR-142, miR-181a, miR-191, miR-148a, miR-7, miR-10, miR-125b, miR-132, miR-212, miR-137, miR-184, miR-200, miR-18, miR-21, or miR-302a.

43. The method of claim 32, wherein the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:

26. SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:

31. SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:

34. SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO 54, SEQ ID NO:55, SEQ ID NO:

56. SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:

59. SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO: 72.PATENT Attorney Docket No.: 048537-663001 WO44. The method of claim 32, wherein the apoptotic domain is a caspase-9 protein, a caspase-3 protein, a caspase-8 protein, a tumor necrosis factor (TNF) protein, a CD95-ligand protein, or a TNF-related apoptosis-inducing ligand (TRAIL) protein.

45. The method of claim 32, wherein the dividing further comprises differentiating the plurality of recombinant pluripotent stem cells within the first period of time.

46. The method of claim 32, wherein the first period of time is betw een about 1 week to about 12 w eeks.

47. The method of claim 32, further comprising isolating the mass of recombinant cells from the subject after the first period of time.

48. The method of claim 32, wherein the nucleic acid is within the genome of each recombinant pluripotent stem cell.

49. The method of claim 48, wherein the nucleic acid is within the adeno-associated virus integration site 1 (AAVS 1) locus of the genome of each recombinant pluripotent stem cell.

50. The method of claim 32, wherein the mass of recombinant cells is an organoid.

51. A method for inducing apoptosis in a first portion of recombinant cells in a mass of recombinant cells, the method comprising: (a) culturing a mass of recombinant cells in vitro for a first period of time, (b) contacting the mass of recombinant cells with a compound; and (b) culturing the mass of recombinant cells for a second period of time in the presence of the compound,wherein each recombinant stem cell in the mass of recombinant cells comprises a nucleic acid comprising a first sequence encoding an inducible dimerizing apoptotic protein and a first microRNA (miRNA)-binding sequence, wherein the inducible dimerizing apoptotic protein comprises a compound-inducible dimerizing domain and an apoptotic domain wherein the mass of recombinant cells comprises a first portion of recombinant cells and a second portion of recombinant cells, wherein the second portion of recombinant cells express a miRNA, thereby blocking translation of the inducible dimerizing apoptotic protein,PATENT Attorney Docket No.: 048537-663001 WO and allowing the second portion of recombinant cells to divide within the second period of time, andwherein the first portion of recombinant cells does not express the miRNA, thereby inducing apoptosis in the first portion of recombinant cells in the mass of recombinant cells.

52. The method of claim 51, wherein the nucleic acid comprises from 5' to 3', the inducible dimerizing apoptotic protein and the first microRNA (miRNA)-binding sequence.

53. The method of claim 51, further comprising a second miRNA-binding sequence, a third miRNA-binding sequence, and a fourth miRNA-binding sequence.

54. The method of claim 53, wherein the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence are the same as the first miRNA-binding sequence.

55. The method of claim 53, wherein the nucleic acid comprises from 5' to 3', the inducible dimerizing apoptotic protein, the first microRNA (miRNA)-binding sequence, the second miRNA-binding sequence, the third miRNA-binding sequence, and the fourth miRNA-binding sequence.

56. The method of claim 51, wherein the compound is a small molecule compound.

57. The method of claim 56, wherein the small molecule is a drug compound.

58. The method of claim 57, wherein the drug compound is AP20187, rimiducid (AP1903). AP21967, rapamycin, gibberellic acid, tamoxifen, lenalidomide, pomalidomide, A1331852, A-1155463, or TMP-POM-7c.

59. The method of claim 51, wherein the compound-inducible dimerizing domain is a drug-mediated dimerization version B (DmrB) domain, a FK506-binding protein (FKBP) domain, a FKBP-rapamycin-binding (FRB) domain, a gibberellin-responsive receptor domain, a tamoxifen-responsive estrogen receptor domain, a cerebl on-binding domain, a B-cell lymphoma (Bel) interaction domain, or a dihydrofolate reductase domain.

60. The method of claim 51, wherein the miRNA is a hepatic miRNA, a pancreatic miRNA, a cardiac muscle miRNA, a neural miRNA, a glial miRNA, a skeletalPATENT Attorney Docket No.: 048537-663001 WO muscle miRNA, a lung miRNA, a cartilage miRNA, a bone miRNA, a vascular smooth muscle miRNA, an endothelial miRNA, a hematopoietic miRNA, a myeloid miRNA, a pluripotent stem cell miRNA, or an epithelial miRNA.

61. The method of claim 51, wherein the miRNA is miR-192, miR-194, miR-122, miR-375, miR-708, miR-216a, miR-1, miR-133a, miR-124, miR-9, miR-218, miR-219a, miR-216a, miR-133a, miR-17, miR-125, miR-338, miR-128, miR-204, miR-211, miR-203, miR-96, miR-206, miR-145. miR-143, miR-208a. miR-140, miR-199, miR-214, miR-126. miR-451, miR-223, miR-130a, miR-142, miR-181a, miR-191, miR-148a, miR-7, miR-10, miR-125b, miR-132, miR-212, miR-137, miR-184, miR-200, miR-18, miR-21, or miR-302a.

62. The method of claim 51, wherein the miRNA-binding domain includes the nucleotide sequence of SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:

39. SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:

42. SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:

56. SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:

60. SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:

63. SEQ ID NO:64, SEQ ID NO:

65. SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:71, or SEQ ID NO:72.

63. The method of claim 51, wherein the apoptotic domain is a caspase-9 protein, a caspase-3 protein, a caspase-8 protein, a tumor necrosis factor (TNF) protein, a CD95-ligand protein, or a TNF-related apoptosis-inducing ligand (TRAIL) protein.

64. The method of claim 51, wherein the culturing of step (a) further comprises allowing the mass of recombinant cells to divide within the first period of time.

65. The method of claim 64, wherein the dividing of step (a) further comprises differentiating the mass of recombinant cells within the first period of time.PATENT Attorney Docket No.: 048537-663001 WO66. The method of claim 51, wherein the culturing of step (c) further comprises allowing the second portion of recombinant cells in the mass of recombinant cells to divide during the second period of time.

67. The method of claim 66, wherein the dividing of step (c) further comprises differentiating the mass of recombinant cells within the first period of time.

68. The method of claim 51, wherein the first period of time is betw een about 1 week to about 12 months.

69. The method of claim 51, wherein the second period of time is between about 1 week to about 89 months.

70. The method of claim 51, further comprising administering the second portion of recombinant cells of the mass of recombinant cells to a subject in need thereof.

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