Non-viral gene delivery system compositions

Abstract

The present invention generally relates at least in part to compositions comprising non-viral vector gene therapies that can provide a means of enhancing rate and efficiency of transport to the nucleus. Also provided herein at least in part are non-virally delivered DNA compositions that exhibit nuclear transport and can be used for the treatment of a broad range of pathologies.

Description

[0001] NON— VIRAL GENE DELIVERY SYSTEM COMPOSITIONS

[0002] RELATED APPLICATIONS

[0003] This application claims the benefit of priority under 35 U. S. C. § 119 (e) of U. S. Provisional Application Serial No. 63 / 713, 615, filed on October 30, 2024, the entire contents of which are incorporated herein by reference.

[0004] FIELD OF THE INVENTION

[0005] The present invention generally relates at least in part to compositions comprising non-viral vector gene therapies that can provide a means of enhancing rate and efficiency of transport to the nucleus. Also provided herein at least in part are non-virally delivered DNA compositions that exhibit nuclear transport and can be used for the treatment of a broad range of pathologies.

[0006] SUMMARY OF THE INVENTION

[0007] Gene therapy is a major therapeutic modality that can enable curative treatment of a broad range of conditions by replacing or augmenting genes, or enabling the production of therapeutic proteins directly inside the body. In a DNA gene therapy, generally, the genetic cargo is delivered using a vector that enables transport of the nucleic acid to the nucleus, where it can be transcribed for downstream therapeutic activity. Most clinical trials and approved products have delivered DNA using viral vectors such as adeno associated virus, herpes simplex virus, adenovirus, and lentivirus; such vectors can be effective at ensuring the therapeutic DNA ends up in the nucleus of the cell being treated or the cell producing the therapeutic protein. However, although traditional viral vector gene therapies have seen a number of successes in clinical studies, they are expensive, antigenic, and not dose-adjustable. Non-viral vectors have a number of advantages over viral vectors including cost, non-antigenicity, potential for dose adjustability, and the ability to deliver a large genetic cassette size. However, DNA cassettes delivered to the cytoplasm by non-viral vectors can be rate- and size-limited in their transport to the nucleus. Thus, provided herein are compositions and methods that can address the foregoing issues. The present invention provides at least in part means of enhancing rate and efficiency of nuclear transport of non-virally delivered DNA. The compositions and methods provided herein can be used for the treatment of mammalian and animal pathologies.

[0008] In an aspect is a therapeutic non-viral gene delivery system for the treatment of human or veterinary pathologies comprised of:

[0009] A. one or more DNA cassettes encoding one or more therapeutic transgenes or therapeutic non-coding DNA regions, and one or more protein binding stretches of DNA,

[0010] B. one or more non-covalently attached peptides or hybrid peptides comprised of a nuclear localization sequence, spacer, and a DNA binding stretch of amino acid, which binds to one or more of the proteinbinding stretches from the DNA cassette, and

[0011] C. with an overall composition such that the stoichiometric ratio of protein binding sites to peptide molecules per non-viral gene delivery particle exceeds a critical pairing number.

[0012] In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part from at least a part of KRGRKP. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of IRKKRGRKPLPPEQKAARRPV. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of a DEXX motif. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of a DEAH, DEAD, or DECH, sequence. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of LXXLL motifs such as LHTLL, LHKLL, or LRYLL. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of known motifs with stretches of basic amino acids. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of KRFARADKRGKLPR, KIEPSKPTATRKRRWSAPETRKLEKSEDEPPLTLPKPSL, PKGRQRK, or KPRRIRKPR. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of a general monopartite sequence, such as K (K / R) X (K / R). In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence includes the motif K (K / R) X (K / R). In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of a general bipartite sequence, such as

[0013] R / K (X) 10-12KRXK. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of

[0014] RRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAE. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of EYQSAIKVEPASPP YYSEKTQLYNRPHEEPSNSLMAI. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of PAAKRVKLD. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of SQKHLQINQTFEELRLVT. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of DEXX. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of LXXLL. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of GKKKKGKPGKRREQRKKKRRT. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of KIEPSKPTATRKRRWSAPETRKLEKSEDEPPLTLPKPSL. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of RKPVTAQERQREREEKRRRRQERAKEREKRRQERER. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of RNKKKK. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of KRPACTLKPECVQQLLVCSQEAKK. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of PKKKRKV. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of CYGSKNTGAKKRKIDDA. In one embodiment of anyone of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of RKKRRQRRR. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of RQARRNRRRRWR. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of KRMNAFMVWAQAARRK. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of KARTPIQKHWRPTVLTEGPPVKIRETGEWEKA. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of KRPAATKKAGQAKKK. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of KRKKEMANKSAPEAKKKK. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of APTKRKGS. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of KQRDAEHRDRTKKKKRSRSRDRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNKVKSRY RSRSRSQSPPKDRKDRDK. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of MSDYGTAR. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of PRRTTRRHPNTQQRASKKKPK. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of GRNRAPELGAPGIQKKKR. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of KLGPRKATGRW. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of PAKRPRETPSPADPPGGASKPRK. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of RLNDAIIKRHVLVLSEYADLKYLGFEKYKFFEY. In one embodiment of any one of the compositions or methods provided herein, the nuclear localization sequence is comprised at least in part of at least a part of

[0015] RRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAE, EYQSAIKVEPASPPYYSEKTQLYNRPHEEPSNSLMAI, PAAKRVKLD, SQKHLQINQTFEELRLVT, SQKHLQINQTFEELRLVT, SQKHLQINQRFEELRLIT, DEXX, DEAH, DEAD, DECH, LXXLL, LHTLL, LHKLL, LRYLL, KRFARADKRGKLPR, KIEPSKPTATRKRRWSAPETRKLEKSEDEPPLTLPKPSL, PKGRQRK, KPRRIRKPR, PKPS, SKL, PKKKRKV, K (K / R) X (K / R), PKLKRQ, RPRK, RRARRPRG, R / K (X) 10-12KRXK, GKRKLITSEEERSPAKRGRKS, KGKKGRTQKEKKAARARSKGKN, KRCAAGVGGGPAGCPAPGSTPLKKPRR,

[0016] RKPVTAQERQREREE KRRRRQE RAKE REKRRQERER, RSGGNHRRNGRGGRGGYNRRNNGYHPY, TLLLRETMNNLGVSDHAVLSRKTPQP Y, P GKMDKGEHRQERRDRP Y, GKKKKGKP GKRREQRKKKRRT,

[0017] S ANKVTKNKSNS SP YLNKRKGKP GP D S, VHSHKKKKIPTSPTFTTPKTLTLRRQPKYPRKSAPRRNKLDHY, RKHKTNRKPR, NRRAKAKR, RNKKKK, RKVIK, Rrmkwkk, Rvhpyqr, Krpactlkpecvqqllvcsqeakk, Pkkkrkv, gkkrska, kakrqr, rgrrrrqr, rkrrr, ppvkrerts, pylnkrkgkp, cygskntgakkrkidda, kkkkrkrek, kkkrrsrek, rkriredrkx- ( 18 ) rkrkr, rrerx ( 4 ) rprkipr, kkkkkeeegegkkk, prprkipr, ppriypqlpsapt, kdcvinkhhrnrcqycrlqr, krx (9) ktkk, apkrksgvskc, rkkrrqrrr, rqarrnrrrrwr, mpktrrrprrsqrkrppt, krpmnaf ivwsrdqrrk, prrk, krmnafmvwaqaarrk, prrrk, kartpiqkhwrptvltegppvkiretgeweka, pprkkrtvv, ykrpckrsf irf i, Ikdvrkrklgpgh, rkprp, rkrkkkraaeddedddvdtkkqk, grkrkkrt, kkkqkk, rekkekeqkekca, lekkvkkkf dwca, tekkqgksilydca, sdkkvrsrlieca, Ikrklqr, rrkgkek, ckrkttnadrrka, vneafetlkrc, mpteervrkrkesnresarrsryrkaahlk, kvnsrkrrkevpgpngateed, prrgpr, prgrrqpipkarqp, krsaeggnppkplkklr, krkx (11) kkkskk, eylsrkgklel, pkrprdrhdgelggrkrarg, krpaatkkagqakkk, krkkemanksapeakkkk, rkrafhgddpf gegppddkk, gggx (3) knrrx (6) rggrn, ynnqssnf gpmkggn, paakrvkld, krpaedmeeeqaf krsr, sxgtkrsyxxm, mnkipkdllnpg, pkkared, vsrkrpr, aptkrkgs, pnkkkrk, eedgpqkkkrrl, pllkkikq, ppqkkiks, pqpkkkp, skrvakrkl, ikyfkkfpkd, ktrkhrg, khrkhpg, pqsrkklr, hrkyeaprhx ( 6) prkr, kkekkkskk, QRDAEHRDRTKKKKRSRSRDRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNKVKSRYR SRSRSQSPPKDRKDRDK, RDRTKKKKRSRSRDRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNKVKSRYRSRSRSQ SPPKDRKDRDKY, KKRIR, KRKYR, PKRRK, KRRP, KKKLKK, MSDYGTAR, IEWESVLT, QKDSDSKL, KKGKDEWF, MMPNKVRKIGELVRYLNTNPVGGLLEYARSHGFAAEFKLVDQSGPPHEPKFVYQAKVGGRWF PAVCAHSKKQGKQEAADAALRVLIGENEKAER, LKRQQRMIKNRESACQSRRKKKEYLQGLEARLQAVLADNQQLRRENAALRRRLEALLAENSE

[0018] L, VLRRQQRMIKNRESACQSRKKKKEYMLGLEARLKAALSENEQLKKENGTLKRQLDEWSENQ RL, PRRTTRRHPNTQQRASKKKPK, KKRK, NSLLVPDSLRGTDKRRNGPEFSNDIKKRKVDDKDSSHYDSDGDKSDDNLWDVSNEDPSSPR ASPAHSP, KQRA, ASPSPPESLVEEERPSGPGGGGKQRADEKEPSGPYESDEDKSDYNLWDEDQPSEPPSPATT

[0019] P, KKRK, NSVSPSESLRASEKHRGSADYSMEAKKRKAEEKDSLSRYDSDGDKSDDLWDVSNEDPATPR VSPAHSP,

[0020] SSVSPSASFRGAEKHRNSADYSSESKKQKTEEKEIAARYDSDGEKSDDNLWDVSNEDPSSP RGSPAHSP, RRMKWKK, GSRKR, KQKQRFEEKRFK, GAVAED,

[0021] GRNRAP E LGAP G I QKKKR,

[0022] ECTRGGFCNFMHLRP I SQNLQRQLYGRGPRRRSPPRFHTGHHPRERNHRCSPDHWHGRF, KGPRAKVAKLNIQSLSPVKKKKMVPGALGVPADLAPVDVEFSFPKFSRLRRGLKAEAVKGPV PAAPARRRLQL, PRLRVR, KVKTKKSTK, RGPEPARETPAKLEPKPIIPKAEPRAKARKTEARGLTKAGAKKKARK, PAKLEPKPIIPKAEPRAKARKTEARGLTKAGAKKKARKE, KKRPSR, and KKR.

[0023] In one embodiment of any one of the compositions or methods provided herein, the space is comprised at least in part of at least a part of a peptide bond to up to 42 amino acids. In one embodiment of any one of the compositions or methods provided herein, the space is comprised at least in part of at least a part of a disordered stretch of amino acids 6 to 42 amino acids in length. In one embodiment of any one of the compositions or methods provided herein, the space is comprised at least in part of at least a part of a disordered stretch of amino acids 6 to 36 amino acids in length. In one embodiment of any one of the compositions or methods provided herein, the space is comprised at least in part of at least a part of a disordered stretch of amino acids 6 to 32 amino acids in length. In one embodiment of any one of the compositions or methods provided herein, the space is comprised at least in part of at least a part of a disordered stretch of amino acids 6 to 26 amino acids in length. In one embodiment of any one of the compositions or methods provided herein, the space is comprised at least in part of a disordered domain rich in one or more of glycine, serine, proline, glutamine, asparagine, lysine, arginine, glutamic acid, or aspartic acid. In one embodiment of any one of the compositions or methods provided herein, the space is comprised at least in part of at least a part of KSKSSSSSSSSTSS. In one embodiment of any one of the compositions or methods provided herein, the space is comprised at least in part of at least a part of LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES, AKKSKTAAKKNDKEAAG, RNSSKCKSKPQIAALKEETEEEVQDTRL, SSKAPPPSLPSPSRLPG, GRDELGGGRRPGTSPALLQGTAE, AKAEAGAEAGGGAGPGAEDEAGRGAVGDPELGDPPAAPQ, EASQSHLRN, KKIKGIQQATTGVSQETSENPGNKTIVPATLPQ, DEKTEESDTDRLLSSDHEKSHSNLGV, AGEGGPP, HEXXHXXG, NEXXSD, GX5EX7REUXEEXGU U = bulky hydrophobic, PVPSTPPTPSPSTPPTPSPSC, PVPX ( 1-12 ) PPPPC, EPKSCDKTHT, CPPCP, APELLGGP, ERK, CCVECPPCP, APPVAXGP, ELKTPLGDTTHT, CPRCP, EPKSCDTPPPCPRCP, APELLGGP, ESKYGX ( 1-5 ) PP, CPSCP, APEFLGGP, RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNT, GTELSVKPNLNKVFPPEV, HXXG, AEEHTDLEAQ, HXXXH, SDQEAKPSTEDLG, QTGGHSTV, GGGGS, GGGGSGGGGS, GGGGSGGGGSGGGGS, GSAGSAAGSGEF, HHHH, and GGGGSGGGGSGGGGSGGGGS. In one embodiment of any one of the compositions or methods provided herein, the space is derived from proteins with high disorder propensity. In one embodiment of any one of the compositions or methods provided herein, the space is derived predominantly from proteins with high disorder propensity. In one embodiment of any one of the compositions or methods provided herein, the space is derived from an amino acid stretch where at least half of the amino acids in a spacer sequence are derived from amino acids with disorder propensity of 0.4 or greater. In one embodiment of any one of the compositions or methods provided herein, the space is derived from an amino acid stretch where at least half of the amino acids in the spacer sequence are derived from amino acids with disorder propensity of 0.43 or greater.

[0024] In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of a protein that contains a DNA-binding region. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of RREKNKVAAARCRNKK. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of NKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTLDPDSYNMFENGSFLRRRRR. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of a protein that is moderately to highly expressed in adipocytes and that contains a DNA-binding region. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of

[0025] SGFHYGVHACEGCKGFFRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAI RFGRMPQAEKEK. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of NHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAK. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of KSNPSKRHRD. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of RERNNIAVRKSR. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of KRRHRTTFTSLQLEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRK. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of RRSKNRIAAQRCRKRK. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of KTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVME YHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPV WIVHGSQ. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of RGNVTSLSLSSNRIHHLHDSDFAH, RGNVTSLSLSSNRIHHLHDSDFAHLPSLRHLNLKWNCPPVGLSPMHFPC, HLPSLRHLNLKWNCPPVGLSPMHFPC, VPTLEELNLSYNNIMTVPALPKSLISLSLSHTNILMLDSASLAGLHALRFLFMDGNCYYKNP CRQALEV, LGNLTHLSLKYNNLTWPRNLPSS, LGNLTHLSLKYNNLTWPRNLPSSLEYLLLSYNRIVKLAPEDLANLTALRVLDVGGNCRRCD HAPNPCMEC, LSRLEGLVLKDSSLSWLNASWFRGLGNLRVLDLSENFLYKCITKTKAFQGLTQLRKLNLSFN YQKRVSFAHLSL, LVALKELDMHGIFFRSLDETTLRPLARLPMLQTLRLQMNFINQAQLGIFRAFPGLRYVDLSD NRISGASELTATMGEA, CSTLNFTLDLSRNNLVTVQPEMFAQLSHLQCLRLSHNCISQAVNGSQFLPLTGLQVLDLSHN KLDLYHEHSFTELPRLEALDLSYNSQPFGMQGVGHNFSFVAHLRTLRHLSLAHNNIHSQVSQ QLCSTSLRALDFSGNALGHMWAEGDLYLH, LSGLIWLDLSQNRLHTLLPQTLRNLPKSLQVLRLRDNYLAFFKWWSLHFLPKLEVLDLAGNQ LKALTNGSLPAGTRLRRLDVSCNSISFVAPGFFS, xLxxLxLxxNxLxxLPxxxFx, GFHYGVHACEGCKGFFRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIR FGRMPQAEKEK, SGFHYGVHACEGCKGFFRRTIRMKLEYEKCERSCKIQKKNRNKCQYCRFQKCLALGMSHNAI RFGRMPEAEK, SGYHYGVHACEGCKGFFRRTIRLKLVYDKCDRSCKIQKKNRNKCQYCRFHKCLSVGMSHNAI RFGRMPRSEKAKLKAEILTCEHDIEDSETADLKSLAKR, SGYHYGVSACEGCKGFFRRSIQKNMI YTCHRDKNCVINKVTRNRCQYCRLQKCFEVGMSKES VRNDRNKKKKETSKQECTESYEMTAELDDLTEKIRKAHQETFPSLCQLGKYTTNSSADHRVR

[0026] r

[0027] SGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCI INKVTRNRCQYCRLQKCFEVGMSKES VRNDRNKKKKEV,

[0028] SGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCI INKVTRNRCQYCRLQKCFEVGMSKEA VRNDRNKKKKVKEEGSPDSYE,

[0029] SGKHYGVYSCEGCKGFFKRTIRKDLI YTCRDNKDCLIDKRQRNRCQYCRYQKCLVMGMKREA VQEERQRSRERA, SGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMGMKREA VQEERQRGKDRN, SGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKKCLSVGMSRD AVRFGRIPKREKQ, SGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCVMDMYMRRKCQECRLRKCKEMGMLAEC MYTGLLTEIQCKSKRLRKNVKQHADQTVNEDSEGRDLRQVTSTTKSCREKTELTPDQQTLLH FIMDSYNKQRMPQEITNKILKEELSAEENFLILTEMATNHVQVLVEFTKKLPGFQTLDHEDQ IALLKGSAVEAMFLRSAEIFNKKLPSGHSDLLEER, SGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCVMDMYMRRKCQECRLRKCKEMGMLAEC MYTGLLTEIQCKSKRLRKNVKQHADQTVNEDSEGRDLR, SGFHYNVLSCEGCKGFFRRSWRGGARRYACRGGGTCQMDAFMRRKCQQCRLRKCKEAGMRE QCVLSEEQIRKKKIRKQQQESQSQSQSPVGPQGS, SGFHYGVHACEGCKGFFRRSIQQNIQYKRCLKNENCSIVRINRNRCQQCRFKKCLSVGMSRD AVRFGRIP, SGKHYGQFTCEGCKSFFKRSVRRNLTYTCRANRNCPIDQHHRNQCQYCRLKKCLKVGMRREA VQRGRMP, SGKHYGQFTCEGCKSFFKRSVRRNLSYTCRANRNCPIDQHHRNQCQYCRLKKCLKVGMRREA VQRGRMP, SGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKKCLSVGMSRD AVRFGRIPKREKQ, SGIHYGVITCEGCKGFFRRSQQNNASYSCPRQRNCLIDRTNRNRCQHCRLQKCLALGMSRDA VKFGRMSKKQ, SGIHYGVITCEGCKGFFRRSQQSNATYSCPRQKNCLIDRTSRNRCQHCRLQKCLAVGMSRDA VKFGRMSKKQR, SGIHYGVITCEGCKGFFRRSQRCNAAYSCTRQQNCPIDRTSRNRCQHCRLQKCLALGMSRDA VKFGR, KVKWTHEEDEQLRALVRQFGQQDWKFLASHFPNRTDQQCQYRWLRVLNPDLVKGPWTKEEDQ KVIELVKKYGTKQWTLIAKHLKGRLGKQCRERWHNHLNPEVKKSCWTEEEDRI ICEAHKVLG NRWAE I AKMLP GRTDNAVKNHWNS T I KR, KTRWTREEDEKLKKLVEQNGTDDWKVIANYLPNRTDVQCQHRWQKVLNPELIKGPWTKEEDQ RVIELVQKYGPKRWSVIAKHLKGRIGKQCRERWHNHLNPEVKKTSWTEEEDRI I YQAHKRLG NRWAEIAKLLPGRTDNAIKNHWNSTMRR, DKGKEKPTDMQNFGLRTDMYTKKNVPSKSKAAASATREWTEQETLLLLEALEMYKDDWNKVS EHVGSRTQDECILHFLR, RLAANARERRRMHGLNHAFDQLRNVIPSFNNDKKLSK, PHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHL, NHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAK, KSNPSKRHRD, RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASR, RNAANARERARM, RLKINSRERKRM, RLMKNREAARECR, RRERNKIAAAKCRNKK, RKLKNRVAAQTARDRK, RYKNNEAAKRSR, RRRKNNMAAKRSR, RERNNIAVRKSR, RKIKNKISAQESR, RREKNKVAAARCRNKK, RREKNRIAAQKSRQRQ, KKRGIFPKVATNIMRAWLFQHLTHP YPSEEQKKQLAQDTGLTILQVNNWFINARRR, KRKRRGNLPKESVKILRDWLYLHRYNAYPSEQEKLSLSGQTNLSVLQICNWFINARRR, PKRPRTILTTQQRRAFKASFEVSSKPCRKVRETLAAETGLSVRWQVWFQNQRAKMKK, RSIWDGEETSYCFKEKSRSVLREWYAHNPYPSPREKRELAEATGLTTTQVSNWFKNRRQRDR

[0030] A, TKRRGPRTTIKAKQLETLKAAFAATPKPTRHIREQLAQETGLNMRVIQVWFQNRRSKERRMK QLSALGAR, KRRHRTTFTSLQLEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRK, SQGSVSEILARPKPWRKLTVKGKEPFIKMKQFLSDEQNVLALRTIQVRQRGSITPRIRTPET GSDDAIKSILEQAKKEIESQKGGEPKTSVAPLSIANGTTPASTSEDAIKSILEQARREMQAQ QQALLEMEVAPRGRSVPPSPPERPSLATASQNGAPALVKQEEGSGGPAQAPLPVLSPAAFVQ SI IRKVKSEIGDAGYFDHHWASDRGLLSRP YASVSPSLSSSSSSGYSGQPNGRAWPRGDEAP VPPEDEAAAGAEDEPPRTGELKAEGATAEAGARLPYYPAYVPRTLKPTVPPLTPEQYELYMY REVDTLELTRQVKEKLAKNGICQRIFGEKVLGLSQGSVSDMLSRPKPWSKLTQKGREPFIRM QLWLSDQLGQAVGQQPGASQASPTEPRSSPSPPPSPTEPEKSSQEPLSLSLESSKENQQPEG RSSSSLSGKMYSGSQAPGGIQEIVAMSPELDTYSITKRVKEVLTDNNLGQRLFGESILGLTQ GSVSDLLSRPKPWHKLSLKGREPFVRMQLWLNDPHNVEKLRDMKKLEKKAYLKRRYGLISTG SDSESPATRSECPSPCLQPQDLSLLQIKKPRWLAPEEKEALRKAYQLEP YPSQQTIELLSF QLNLKTNTVINWFHNYRSRMRR,

[0031] KNKRGVLPKHATNIMRSWLFQHLMHP YPTEDEKRQIAAQTNLTLLQVNNWFINARRR, GWKNSIRHNLSLNKCFRKVPRPRDDPGK, SSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWI INPDGGKSGKAPRR, AWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTLDPQSEDMFDNGSFLRRRKR, RPEKPP YSYIALIVMAIQSSPSKRLTLSEI YQFLQARFPFFRGAYQGWKNSVRHNLSLNECF IKLPKGLGRPGKGHYWTIDPASEFMFEEGSFRRRPR, NKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTLDPDSYNMFENGSFLRRRRR, HTASPWNLSPFSKTSIHHGSPGPLSVYPPASSSSLSGGHASPHLFTFPPTPPKDVSPDPSLS TPGSAGSARQDEKECLKYQVPLPDSMKLESSHSRGSMTALGGASSSTHHPITTYPPYVPEYS SGLFPPSSLLGGSPTGFGCKSRPKARSSTGRECVNCGATSTPLWRRDGTGHYLCNACGLYHK MNGQNRPLIKPKRRLSAARRAGTSCANCQTTTTTLWRRNANGDPVCNACGLYYKLHNINRPL TMKKEGIQTRNRK, PLWRRDGTGHYLCNACGLYHKMNGQNRPLIKPTSCANCQTTTTTLWRRNANGDPVCNACGLY YKLHNINRPLTMKKEGIQTRNRKM, PLWRRDGTGHYLCNACGLYSKMNGLSRPLIKPQKRVPSSRRLGLSCANCHTTTTTLWRRNAE GEPVCNACGLYMKLHGVPRPLAMKKEGIQTRKRK, VEEEISRHYRRAHSCYKCRQCSFTAADTQSLLEHFNTVHCQEQDITTANGEEDGHAISTIKE EPKIDFRVYNLLTPDSKMGEPVSESWKREKLEEKDGLKEKVWTESSSDDLRNVTWRGADIL RGSPSYTQASLGLLTPVSGTQEQTKTLRDSPNVEAAHLARPIYGLAVETKGFLQGAPAGGEK SGALPQQYPASGENKSKDESQSLLRRRRGSGVFCANCLTTKTSLWRKNANGGYVCNACGLYQ KLHSTPRPLNI IKQNNGEQI IRRRTRKRLNPEALQAEQLNKQQRGSNEEQVNGSPLERRSED HLTESHQREIPLPSLSKYEAQGSLTKSHSAQQPVLVSQTLDIHKRMQPLHIQIKSPQESTGD PGNSSSVSEGKGSSERGSPIEKYMRPAKHPNYSPPGSPIEKYQYPLFGLPFVHNDFQSEADW LRFWSKYKLSVPGNPHYLSHVPGLPNPCQNYVP YPTFNLPPHFSAVGSDNDIPLDLAIKHSR PGPTANGASKEKTKAPPNVKNEGPLNWKTEKVDRSTQDELSTKCVHCGIVFLDEVMYALHM SCHGDSGPFQCSICQHLCTDKYDFTTHIQR, QEGRLQRKQKNATGGRRHICHECGKSFAQSSGLSKHRRIHTGEKP YECEECGKAFIGSSALV IHQRVHTGEKP YECEECGKAFSHSSDLIKHQRTHTGEKP YECDDCGKTFSQSCSLLEHHRIH TGEKPYQCSMCGKAFRRSSHLLRHQRIHTGDKNVQEPEQGEAWKSRMESQLENVETPMSYKC NECERSFTQNTGLIEHQKIHTGEKPYQCNACGKGFTRISYLVQHQRS, REAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDK, KSNPSKRHRD, RENHSEIERRRRNKMTAYITELSDMVPTCPDK, RGMRFRYECEGRSAGSILGESSTEASKTLPAIELRDCGGLREVEVTACLVWKDWPHRVHPHS LVGKDCTDGICRVRLRPHVSPRHSFNNLGIQCVRKKEIEAAIERKIQLGIDP YNAGSLKNHQ EVDMNWRICFQASYRDQQGQMRRMDPVLSEPVYDKKSTNTSELRICRINKESGPCTGGEEL YLLCDKVQKEDISWFSRASWEGRADFSQADVHR, MSSAIERKSLDPSEEPVDEVLQIPPSLLTCGGCQQNIGDRYFLKAIDQYWHEDCLSCDLCGC RLGEVGRRLYYKLGRKLCRRDYLRLFGQDGLCASCDKRIRAYEMTMRVKDKVYHLECFKCAA CQKHFCVGDRYLLINSDIVCEQDIYEWTKINGMI,

[0032] KRPRTTITAKQLETLKSAYNTSPKPARHVREQLSSETGLDMRWQVWFQNRRAKEKR, PKRPRTILTTQQRRAFKASFEVSSKPCRKVRETLAAETGLSVRWQVWFQNQRAKMKK, NGRPLPDWRQRIVELAHQGVRPCDISRQLRVSHGCVSKILGRYYETGSIKPGVIGGSKPKVATPKWEKIAEYKRQNPTMFAWEIRDRLLAERVCDNDTVPSVSSINRIIR, NGRPLPNAIRLRIVELAQLGIRPCDISRQLRVSHGCVSKILARYNETGSILPGAIGGSKPRV TTPTWKHIRTYKQRDPGIFAWEIRDRLLADGVCDKYNVPSVSSISRILR, KYFKKHEKR, DGRLQVAGRKGFPHVI YARLWRWPDLHKNELKHVKYCQY, DGRLQVSHRK, RRMFPTIRVSFSGVDPEAKYIVLMDIVPVDNKRYRYAYHRSSWLVAGKADPPLPARLYVHPD SPFTGEQLLKQMVSFEKVKLTNNELDQHGHI ILNSMHKYQPRVHI IKKKDHTASLLNLKSEE FRTFIFPETVFTAVTAYQNQLITKLKIDSNPFAKGF, LTTEADSGY, AYRQK, HFARKDLSEADARIFKAWAVARGRWPPSSRGGGPPPEAETAERAGWKTNFRCALRS, RRSKNRIAAQRCRKRK, LHVENYLRHLKMHKLFLCLQCGKTFTQKKNLNRHIRGHMGIRPFQCTVCLKTFTAKSTLQDH LNIHSGDRPYKCHCCDMDFKHKSALKKHLTS, and EKLSRGLRYYYDKNI IHKTAGKR. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is comprised at least in part of at least a part of eenvkRrTHNvLErqRRnelkr,

[0033] eenvkRrTHNvLERqRRNelkRsf f alrdqipelennekapKvvilk, mnvkRrtHNvLERqRRNelkRsf f alrdqipelennekapKvvilk, hmnvkRrtHNvLERqRRNelkRsff alrdqipelennekapKvvilk, serrrNHNiLErqRRndlRssf It IrdhvpelvknekaaKvvilk, tkkkyHSyLErkRRndqRsrf lalrdevpalascsrVsKvmilv, saadkRaHHNaLErkRRdhiKdsfhslrdsvpslqgekasRaqild, errrvRRerNKlAAakCRnrrkeltdf IqaetdkledeksglqreiEelqkq, ekrriRRerNKlAAakCRnrRrelte, ekrriRRerNKmAAakCRnrRreltd, krriRRerNKmAAakSRnrrre,

[0034] cgdkaSGf HYgvhacEGcKGf fRRtirlkliydrcdlncrihkksrNkcqyc, cgdkaSGf HYgvhacEGcKGf fRRtirmkleyekcersckiqkknrNkcqyc, cgdkaSGy HYgvhacEGcKGf fRRtirlklvydkcdrsckiqkknrNkcqyc, scgslNmecrvcgdKaSGFHYgvhacEGcKGf fRRtirmkleyekcersckiqkknrNkcqy c, qarkaFnckycnkeyLSLGAlKMhlRshtlp, cnktySTf SGlaKhkqLhcdaq, ppqvlKtqtkf aatvrllvggklnvhmnppqvkatiiseqqaksllknentrnecsgeilnn cc,

[0035] meyhqatgtlsahf rnmslkrikradrrgaEsvteekftvlf esqf svgsnelvf qvktlsl p, vvviVHGSQdhnat,

[0036] ppqvlKtqtkfaatvrllvggklnvhmnppqvkatiiseqqaksllknentrndysgei Inn cc,

[0037] meyhqatgtlsahf rnmslkrikrsdrrgaEsvteekftilf esqf svggnelvf qvktlsl pvvviVHGSQdnnat,

[0038] ppqvlKtqtkf qagvr fl Iglrf Igapakppl vradmvtekqarels vpqgpgagae st gei in,

[0039] tvplensipgnccsalf knlllkkikrcerkgtEsvteekcavlf sasftlgpgklpiqlqa 1, slplvviVHGNQdnnak,

[0040] ppqvlKtqtkf qagvr fl Iglrf Ipakpplvradmvt ekqarele st gei innt vplens ip gn,

[0041] csalf knlllkkikrcerkgtEsvteekcavlf sas ft IgpgklpiqlqalslplvviVHGN Qdnnak,

[0042] ppqvlKtqtkf qagvr fl Iglrf pakpplvradmvt ekqarele st gei innt vplens ipg nc,

[0043] salf knlllkkikrcEgtesvteekcavlf sasftlgpgklpiqlqalslplvviVHGNQdn nak,

[0044] ppqvlKtqtkf qagvr fl Iglrf Igpakpplvradmvt ekqaret gei innt vplens ipgn cc,

[0045] salf knlllkkikrcerkgtEsvteekcavlf sas ft IglpiqlqalslplvviVHGNQdnn ak,

[0046] ppqvlKtqtkf qagvr fl Iglrf Igapakppl vradmvt ekqaret gei innt vplens ipg nc,

[0047] salf knlllkkikrcerkgtEsvteekcavlf sas ft IgppiqlqalslplvviVHGNQdnn ak,

[0048] ppqvlKtqtkf qagvr fl Iglrf Igapakppl vradmvt ekqaret gei innt vplens ipg nc,

[0049] csalf knlllkkikrcEgtesvteekcavlf sas ft Igpiqlqal slplvviVHGNQdnnak, ItkteHpkSsf rlhRMrrMgsasr, chkmySNKGTIRVhyktv, neyrvRRerNNiAVrkSRdkakq, leyrlRReRNNiAVrKSRdkakr, eyrlrRerNNiAVrkSRdkakr, eykirRerNNiAVrkSRdkakm, ssgprTrklkk, kpkkkNpnkeDKRPRtaftaeqlqrlkaef qtnrylteqrrqslaqelslneSQiKIwfQNk rAKikKatgnk,

[0050] dldrpKRTRt sftaeqlyrlemef qrcqyvvgrertelarqlnlseTQvKVWfQNRrTKqkK dqgkd,

[0051] dldrpKRTRt sftaeqlyrlemef qrcqyvvgrertelarqlnlseTQvKVwfQNrrTKqkK dqsrd,

[0052] IhcrrKRRHRtiftdeqlealenlf qetkypdvgtreqlarkvhlreEKvEVwfKNrrAKwr Rqkrss,

[0053] pgsqrRtRRHRtif seeqlqalealfvqnqypdvstrerlagrirlreERvEVwfKNrrAKw rHqkras,

[0054] harstRKKRcpytkyqtlelekef If nmyltrdrryevarvlnlteRQvKIwfQNrrMKmkK mnkek,

[0055] harssRKKRcpytkyqtlelekef If nmyltrdrrhevarllnlseRQvKIwfQNrrMKMkK mnkeq,

[0056] harstRKKRcpytkhqtlelekef If nmyltrdrryevarllnlteRQvKIwfQNrrMKMkK inkdr,

[0057] harssRKKRcpytkyqtlelekef If nmyltrdrrhevarllnlseRQvKIwfQNrrMKMkK mnkeq,

[0058] harstRKKRcpytkyqtlelekef If nmyltrdrryevarilnlteRQvKIwfQNrrmkm, taksgRKKRcpytkhqtlelekef If nmyltrerrleisktinltdRQvKIwfQNrrMKlkK mnren, ekeskEeiksd,

[0059] taksgRKKRcpytkhqtlelekef If nmyltrerrleisrsvhltdRQvKIwfQNrrMKlkK mnren, IgsgqRqsASeREklRMrtlar, paggqRqsASeREKIRMrtlar, msvqrRrkaSeREklRMrtlad,

[0060] ikktrRlkANnRERnRMhnlnaaldalrevlpt fpedakltKietlr, itkagRrmfpamrvkisgldphqqyyiamdivpvdnkryryvyhsskwmvagnadspvpprvyi,

[0061] pdspasgetwmrqvisf dklkltnnelddqghiilhsmhkyqprvhvirkdcgddlspikpv psgegvkaf sfpetvfttVTAyqnqqitrlkidrnpFakGFrdsgr, itkagRrmfpamrvkitgldphqqyyiamdivpvdnkryryvyhsskwmvagnadspvpprv yihpdslasgdtwmrqvvSf dKLkltnnelddqghiilhsmhkyqprvhvirkdf ssdlspt kpvpvgdgvkt f nfpetvfttvTAyqnqqitrlkidrnpFakGFrdsgr, itkagRrmfpamrvkisgldphqqyyiamdivpvdnkryryvyhsskwmvagnadspvpprv yihpdspasgetwmrqvisf dklkltnnelddqghiilhsmhkyqprvhvirkdcgddlspi kpvpsgegvkaf sfpetvfttvTAyqnqqitrlkidrnpFakGFrdsgr, itkagRrmfpamrvkitgldphqqyyiamdivpvdnkryryvyhsskwmvagnadspvpprv yihpdslasgdtwmrqvvSf dKLkltnnelddqghiilhsmhkyqprvhvirkdf ssdlspt kpvpvgdgvkt f nfpetvfttvTAyqnqqitrlkidrnpFakGFrdsgr, itksgRrmfptirvsf sgvdpeakyivlmdivpvdnkryryayhrsswlvagkadpplparl yvhpdspftgeqllkqmvsf ekvkltnneldqhghiilnsmhkyqprvhiikkkdhtaslln Ikseef rt f ifpetvftavTAyqnqlitklKidsnpFakGFrdssr, vtkagRrmfpt f qvklf gmdpmadymllmdfvpvddkryryafhssswlvagkadpatpgrv hyhpdspakgaqwmkqivsf dklkltnnllddnghiilnsmhryqprfhvvyvdprkdseky aeenf kt fvf eetrftavTAyqnhritqlkiasnpFakGF,

[0062] vtkagRrmfpt f qvklf gmdpmadymllmdfvpvddkryryafhssswlvagkadpatpgrv hyhpdspakgaqwmkqivsf dklkltnnllddnghiilnsmhryqprfhvvyvdprenf kt f vf eetrftavTAyqnhritqlkiasnpFakGF, or

[0063] vtkagRrmfpt f qvklf gmdpmadymllmdfvpvddkryryafhssswlvagkadpatpgrv hyhpdspakgaqwmkqivsf dklkltnnllddnghiilnsmhryqprfhvvyvdprkdseky aeenf kt fvf eetrftavTAyqnhritqlkiasnpFakGFrdcdp. In one embodiment of any one of the compositions or methods provided herein, the DNA binding stretch of amino acids is derived at least in part of at least a part of the following protein domain sequences: C2H2 type zinc finger, Zinc finger, C2H2 type, Zinc finger double domain, C2H2 type zinc finger, Homeobox domain, Myb like DNA binding domain, Helix loop helix DNA binding domain, Zinc finger, C4 type (two domains), Myb like DNA binding domain, bZIP transcription factor, Basic region leucine zipper, Ligand binding domain of nuclear hormone receptor, Zinc finger of C2H2 type, Homeobox KN domain, HMG (high mobility group) box, Domain of unknown function (DUF1898), Fork head domain, Ets domain, AP2 domain, GATA zinc finger, Pou domain N terminal to homeobox domain, KRAB box, Fungal Zn (2) Cys (6) binuclear cluster domain, Ankyrin repeat, PAS fold, Rel homology domain (RHD), GTF2I like repeat, LIM domain, C2H2 type zinc finger domain, ' Paired box' domain, MH1 domain, SRF type transcription factor (DNA binding and dimerization domain), AT hook motif, T box, IPT / TIG domain, Ankyrin repeats (3 copies), Interferon regulatory factor transcription factor, BTB / POZ domain, Sterile alpha motif (SAM) / Pointed domain, No apical meristem (NAM) protein, PAS fold, CUT domain, WRKY DNA binding domain, bZIP Maf transcription factor, Fungal specific transcription factor domain, B3 DNA binding domain, Sigma 70, region 4, E2F / DP family winged helix DNA binding domain, Interferon regulatory factor 3, N terminal CTNNB1 binding, Sigma 70 region 2, Ankyrin repeats (many copies), CTF / NF I family transcription modulation region, HSF type DNA binding, P53 DNA binding domain, C2H2 type zinc finger (2 copies), Ankyrin repeat, Helix turn helix, OAR domain, Runt domain, pKID domain, P53 tetramerisation motif, Nuclear factor I protein pre N terminus, Sigma 70 region 3, Response regulator receiver domain, Sigma 70 factor, region 1.2, Transcription factor TFIID (or TATA binding protein, TBP), SH2 domain, MarR family, STAT protein, all alpha domain, STAT protein, DNA binding domain, DM DNA binding domain, RFX DNA binding domain, SCAN domain, MH2 domain, Winged helix DNA binding domain, Tesmin / TSOl like CXC domain, Transcriptional regulatory protein, C terminal, Myb / SANT like DNA binding domain, Dof domain, zinc finger, MerR family regulatory protein, MerR HTH family regulatory protein, MarR family, SAND domain, Transcription factor TFIIB repeat, TCP family transcription factor, Domain of unknown function (DUF3371), PHD finger, Sigma 70, non essential region, Hairy Orange, STAT protein, protein interaction domain, Myogenic Basic domain, Auxin response factor, Bacterial regulatory proteins, gntR family, Bacterial regulatory proteins, luxR family, ARID / BRIGHT DNA binding domain, Transcription factor AP 2, Bacterial regulatory proteins, lacl family, Hepatocyte nuclear factor 1 (HNF 1), N terminus, Holliday junction regulator protein family C terminal repeat, K box region, Myc amino terminal region, PAS domain, Estrogen receptor beta, Zinc finger double stranded RNA binding, Bacterial regulatory helix turn helix proteins, AraC family, Periplasmic binding proteins and sugar binding domain of Lacl family, Periplasmic binding protein like domain, Sigma 70, region 4, Glucocorticoid receptor, Alcohol dehydrogenase transcription factor Myb / SANT like, TEA / ATTS domain family, Runx inhibition domain, Homeodomain leucine zipper encoding, Homez, Myc leucine zipper domain, AUX / IAA family, Winged helix turn helix DNA binding, LAG1, DNA binding, Myb / SANT like DNA binding domain, BED zinc finger, Beta trefoil DNA binding domain, TFIIB zinc binding, GATA type transcription activator, N terminal, Periplasmic binding protein domain, CP2 transcription factor, Paired box protein 2 C terminal, Jun like transcription factor, SBP domain, G box binding protein MFMR, Hox protein A13 N terminal, Histone like transcription factor (CBF / NF Y) and archaeal histone, Forkhead N terminal region, C myb, C terminal, SOX transcription factor, Homeobox associated leucine zipper, GCM motif protein, Wilm's tumor protein, Myogenic determination factor 5, lysR family, Core histone H2A / H2B / H3 / H4, Hox9 activation region, MYB CC type transfactor, LHEQLE motif, MerR, DNA binding, Homeodomain like domain, Seed dormancy control, LMSTEN motif, HTH domain, HNF3 C terminal domain, Androgen receptor, Nuclear receptor repeat, helix turn helix, Psq domain, PBC domain, Zinc finger associated domain (zf AD), Engrailed homeobox C terminal signature domain, Hepatocyte nuclear factor 1 (HNF 1), beta isoform C terminus, Transcription factor protein N terminal, Iron dependent repressor, N terminal DNA binding domain, RFX1 transcription activation region, Maf N terminal region, SAM domain (Sterile alpha motif), CXXC zinc finger domain, Sox developmental protein N terminal, Domain of unknown function (DUF3446), P53 transactivation motif, Oestrogen receptor, Homeobox protein distal less like N terminal, DeoR like helix turn helix domain, Vertebrate heat shock transcription factor, Sp100 domain, Crp like helix turn helix domain, Sox C terminal transactivation domain, LysR substrate binding domain, Transcriptional regulator, Fungal specific transcription factor domain, IQ calmodulin binding motif, Protein of unknown function DUF260, Zinc finger, C3HC4 type (RING finger), PEA3 subfamily ETS domain transcription factor N terminal domain, Nuclear / hormone receptor activator site AF 1, Zinc finger, C3HC4 type (RING finger), PPAR gamma N terminal region, CCAAT binding transcription factor (CBF B / NF YA) subunit B, Cyclic nucleotide binding domain, T box transcription factor, Bacterial regulatory proteins, crp family, Ring finger domain, START domain, Ferric uptake regulator family, Cro / Cl type HTH DNA binding domain, Iron dependent repressor, metal binding and dimerisation domain, bHLH MYC and R2R3 MYB transcription factors N terminal, Bacterial regulatory protein, Fis family, SET domain, Death domain, Hypoxia inducible factor 1, KilA N domain, ' Cold shock' DNA binding domain, Otxl transcription factor, Caudal like protein activation region, FHA domain, Poly (ADP ribose) polymerase and DNA Ligase Zn finger region, HIF 1 alpha C terminal transactivation domain, Protein of unknown function (DUF3528), Helicase conserved C terminal domain, THAP domain, Sugar specific transcriptional regulator TrmB, Arc like DNA binding domain, Arginine repressor, DNA binding domain, Neuronal helix loop helix transcription factor, Epstein Barr virus nuclear antigen 1, DNA binding domain, FeoC like transcriptional regulator, Methyl CpG binding domain, DMRTA motif, Cyclin, N terminal domain, Bacterial regulatory proteins, tetR family, HxlR like helix turn helix, ZF HD protein dimerisation region, BESS motif, Domain of unknown function (DUF4074), Transcriptional regulator PadR like family, linker histone Hl and H5 family, GyrI like small molecule binding domain, Arginine repressor, C terminal domain, MYND finger, Ribbon helix helix protein, copG family, SNF2 family N terminal domain, CCT motif, Basic leucine zipper C terminal, RNA recognition motif, (a. k. a. RRM, RBD, or RNP domain), RNA recognition motif, (a. k. a. RRM, RBD, or RNP domain), Oestrogen type nuclear receptor final C terminal, Ethylene insensitive 3, RNA recognition motif (a. k. a. RRM, RBD, or RNP domain), Helix turn helix domain, Plant zinc cluster domain, Core binding factor beta subunit, Plant protein of unknown function (DUF822), ELK domain, Progesterone receptor, Paired box protein 7, KNOX2 domain, Domain of unknown function (DUF296), Autoinducer binding domain, CG 1 domain, FCD domain, ATPase family associated with various cellular activities (AAA), CoA binding domain, BAH domain, TFIIE alpha subunit, Putative DNA binding protein N terminus, KNOX1 domain, Tc5 transposase DNA binding domain, WRC, TrkA C domain, Hepatocyte nuclear factor 1 (HNF 1), alpha isoform C terminus, HIRAN domain, Zinc knuckle, GA binding protein alpha chain, CarD like / TRCF domain, arsR family, NDT80 / PhoG like DNA binding family, Homeobox prospero like protein (PROX1), Poxvirus D5 protein like, WGR domain, Paired amphipathic helix repeat, F box like, Antitermination protein, PADR1 (NUC008) domain, Ataxin 1 and HBP1 module (AXH), Protein of unknown function, DUF573, hAT family dimerisation domain, pre mRNA splicing factor component, Domain of unknown function (DUF4371), Transcription initiation factor IIF, alpha subunit (TFIIF alpha), NLS binding and DNA binding and dimerisation domains of Nrfl, CodY GAF like domain, Transcriptional activator of glycolytic enzymes, JmjC domain, hydroxylase, BRCA1 C Terminus (BRCT) domain, CASP C terminal, Sigma 54 interaction domain, Poly (ADP ribose) polymerase catalytic domain, DDE superfamily endonuclease, IclR helix turn helix domain, TAZ zinc finger, tify domain, zinc finger of a C2HC type, ECF sigma factor, PRD domain, Domain of unknown function (DUF3432), Penicillinase repressor, Poly (ADP ribose) polymerase, regulatory domain, Trp repressor protein, Herpesvirus ICP4 like protein N terminal region, QLQ, B12 binding domain, FadR C terminal domain, DeoR C terminal sensor domain, Gal4 like dimerisation domain, Brfl like TBP binding domain, E2 (early) protein, C terminal, STE like transcription factor, Tetracycline repressor, C terminal all alpha domain, Nrfl activator activation site binding domain, CodY helix turn helix domain, Bacterial dnaA protein helix turn helix, Copper fist DNA binding domain, Zinc finger, C3HC4 type (RING finger), GAGA binding protein like family, Telomere repeat binding factor (TRF), AAA domain (dynein related subfamily), Transcription factor PAP1, Vertebrate interleukin 3 regulated transcription factor, Aminotransferase class I and II, F box domain, YABBY protein, PAS fold, RNA polymerase Rpbl, domain 5, Divergent CCT motif, Sigma 70 factor, region 1.1, HD ZIP protein N terminus, RNA polymerase Rpbl, domain 4, Bacteriophage CII protein, SKI / SNO / DAC family, CENP B N terminal DNA binding domain, Double sex mab3 related transcription factor 1, UTRA domain, Floricaula / Leafy protein, Zinc knuckle, jmjN domain, RNA polymerase Rpbl, domain 2, RNA polymerase Rpbl, domain 3, Zfx / Zfy transcription activation region, MEKHLA domain, Transcription initiation factor IIF, beta subunit, Type III restriction enzyme, res subunit, Zinc finger, C2HC type, RNA polymerase Rpbl, domain 1, Bromodomain, BAF1 / ABF1 chromatin reorganising factor, NikR C terminal nickel binding domain, POU domain, class 2, associating factor 1, DDT domain, Histone acetylation protein, Transcription factor IIA, alpha / beta subunit, Fungal protein of unknown function (DUF1752), B box zinc finger, Bacterial transcriptional regulator, MULE transposase domain, Creb binding, Bacterial dna Aprotein, c SKI Smad4 binding domain, ROK family, Metal binding domain of Ada, Transcription initiator DNA binding domain IBD, IstB like ATP binding protein, DEAD / DEAH box helicase, Peptidase S24 like, Sporulation initiation factor SpoOA C terminal, Met Apo repressor, MetJ, RWP RK domain, TRCF domain, Chaperone of endosialidase, Zinc finger, ZZ type, FeoA domain, RNA polymerase Rpbl C terminal repeat, BEN domain, Transcription factor AFT, AsnC family, PAS domain, PurA ssDNA and RNA binding protein, MT A70, Zinc finger protein, KIX domain, Minimal binding motif of Hap4 for binding to Hap2 / 3 / 5, Histidine kinase, DNA gyrase B, and HSP90 like ATPase, AsnC type helix turn helix domain, Domain of unknown function (DUF702), Domain of Unknown Function (DUF902), STAT1 TAZ2 binding domain, Inhibitor of growth proteins N terminal histone binding, C terminal domain of methyl CpG binding protein 2 and 3, RNA polymerase beta subunit, Homeobox protein, Putative binding domain, Cupin like domain, TOBE domain, SWIM zinc finger, Putative helix turn helix protein, YlxM / pl3 like, Cytosine specific DNA methyltransferase replication foci domain, Doublesex dimerisation domain, GAGA factor, RNA polymerase Rpb2, domain 3, Domain of unknown function (DUF313), Churchill protein, FAR1 DNA binding domain, RING H2 zinc finger, Rapl, DNA binding, Putative ATPase subunit of terminase (gpP like), AraC like ligand binding domain, GRF zinc finger, RNA polymerase Rpb2, domain 4, Transferrin, Integrase core domain, SPRY domain, AN1 like Zinc finger, SWIRM domain, RNA polymerase Rpb2, domain 6, RNA polymerase Rpb2, domain 5, WD domain, G beta repeat, Helix turn helix domain of resolvase, Centromere protein B dimerisation domain, Signal transducer and activator of transcription 2 C terminal, GRAS family transcription factor, Oxygenase domain of the 2OGFeDO superfamily, QacR like protein, C terminal region, Histone deacetylase domain, Transcription factor DP, LisH, LexA DNA binding domain, RecF / RecN / SMC N terminal domain, Domain of unknown function DUF120, DnaA N terminal domain, RING type zinc finger, LisH dimerisation motif, Brinker DNA binding domain, Amino acid kinase family, RNA polymerase Rpbl, domain 7, Protein kinase domain, N terminal domain of DPF2 / REQ., Transcription factor Vhrl, Glycosyl hydrolase family 14, Domain of unknown function (DUF2028), mTERF, RNA polymerase Rpb2, domain 7, RNA polymerase Rpbl, domain 6, Protein tyrosine kinase, Associated with HOX, AAA domain (Cdc48 subfamily), Fushi tarazu (FTZ), N terminal region, RING variant domain, PB1 domain, CBS domain, RNA polymerase Rpb2, domain 2, Lectin C type domain, Ubiquitin C terminal hydrolase 37 receptor binding site, CAT RNA binding domain, Phosphoribosyl transferase domain, Phi 29 like late genes activator (early protein GP4), Protein of unknown functionDUF134, C 5 cytosine specific DNA methylase, Arginase family, Alpha / beta hydrolase family, Nucleopolyhedrovirus late expression factor 3 (LEF 3), H NS histone family, TFIIE beta subunit core domain, PBP superfamily domain, PLATZ transcription factor, Complexl_LYR like, Histidine kinase, DNA gyrase B, and HSP90 like ATPase, BSD domain, Sec7 domain, Sigma 54 modulation protein / S30EA ribosomal protein, TipAS antibiotic recognition domain, Thiolase, C terminal domain, PCI domain, Zn finger in Ran binding protein and others, DMAP1 binding Domain, Mannitol dehydrogenase Rossmann domain, GAF domain, DNA binding protein S1FA, Protein of unknown function (DUF3591), CW type Zinc Finger, ARC105 or Medl5 subunit of Mediator complex non fungal, Oxidoreductase family, NAD binding Rossmann fold, Semialdehyde dehydrogenase, NAD binding domain, Guanine nucleotide exchange factor in Golgi transport N terminal, Cytochrome C and Quinol oxidase polypeptide I, E2 (early) protein, N terminal, NOPS (NUC059) domain, phosphotransferase system, EIIB, YL1 nuclear protein, KorB domain, 6 0 methylguanine DNA methyltransferase, DNA binding domain, Mannitol dehydrogenase C terminal domain, Poxvirus early transcription factor (VETF), large subunit, GAF domain, Herpesvirus transcription activation factor (transactivator), Leucine Rich repeat, Transcription factor Opil, ATP cone domain, P protein C terminus, DHHC palmitoyltransferase, YsiA like protein, C terminal region, XPA protein N terminal, CoA binding domain, dimerisation domain, Acetyltransferase (GNAT) family, TLC domain, Phosphotransferase system, EIIC, YL1 nuclear protein C terminal domain, Ribosomal protein L16p / L10e, Domain of unknown function (DUF4195), G patch domain, Plus 3 domain, Bacterial purine repressor, N terminal, Rapl C terminal domain, Zinc binding, KH domain, HAMP domain, GAF domain, Tryptophan RNA binding attenuator protein, F / Y rich N terminus, Transcriptional activator TraM, XPA protein C terminus, Exonuclease, Protein of unknown function (DUF619), Pyridine nucleotide disulfide oxidoreductase, His (2) Cys (2) zinc finger, Zinc carboxypeptidase, Bacterial transferase hexapeptide (six repeats), DExH box splicing factor binding site, 6 0 methylguanine DNA methyltransferase, ribonuclease like domain, Bacterial DNA binding protein, OTU like cysteine protease, Mating type protein MAT alpha 1, B block binding subunit of TFIIIC, MamL 1 domain, KH domain, Firmicute transcriptional repressor of class III stress genes (CtsR), Histidine kinase, Zinc finger of the MIZ type in Nse subunit, Metallo beta lactamase superfamily, Basic membrane protein, F / Y rich C terminus, Eukaryotic translation initiation factor eIF2A, UBA / TS N domain, BTB And C terminal Kelch, SAM domain (Sterile alpha motif), Aftl osmotic stress response (OSM) domain, Pyridine nucleotide disulfide oxidoreductase, Interferon induced 35 kDa protein (IFP 35) N terminus, Protein of unknown function (DUF2817), Sin3 binding region of histone deacetylase complex subunit SAP30, HrcA protein C terminal domain, Magnesium chelatase, subunit Chll, Archaeal ATPase, Transcriptional regulator DELLA protein N terminal, Maltose acetyltransferase, Suppressor of cytokine signalling, SI RNA binding domain, 3H domain, ABA / WDS induced protein, Transcription factor CRF1, Domain of unknown function (DUF3518), Recombinase Flp protein N terminus, Beta lactamase superfamily domain, PHD like zinc binding domain, Myelin gene regulatory factorC terminal domain 1, Aldehyde dehydrogenase family, Nuclear pore complex assembly, Putative GTPase activating protein for Arf, Anti repressor SinI, Antidote toxin recognition MazE, SSXRD motif, CBF / Mak21 family, L lysine 6 monooxygenase (NADPH requiring), Adenylate and Guanylate cyclase catalytic domain, Flagellar transcriptional activator (FlhD), PTS system fructose IIA component, AAA domain, Stage III sporulation protein D, Transcription

[0064] f actor / nuclear export subunit protein 2, NusA N terminal domain, Reverse transcriptase like, SMC proteins Flexible Hinge Domain, short chain dehydrogenase, Glycerol 3 phosphate responsive antiterminator, alpha / beta hydrolase fold, Recombinase Flp protein, Domain of unknown function (DUF3425), His Kinase A (phospho acceptor) domain, Family description, PHD zinc finger like domain, PTS HPr component phosphorylation site, DDE superfamily endonuclease, Transcriptional enhancer, Asx hm domain, DnaJ domain, SPFH domain / Band 7 family, Myelin gene regulatory factor C terminal domain 2, Proline dehydrogenase, Cro, Domain of unknown function (DUF4171), CHY zinc finger, Pyridine nucleotide disulfide oxidoreductase, Protein phosphatase 2C, YcdC like protein, C terminal region, Ribosomal protein L35Ae, C5HC2 zinc finger, Transcription and export related complex subunit, Uncharacterized protein family (UPF0121), NusA like KH domain, PAS domain, AAA domain, Domain of unknown function (DUF3594), Alpha / beta hydrolase family, Peptidase family Ml, GDSL like Lipase / Acylhydrolase, Complex 1 protein (LYR family), Winged helix turn helix, Ubiquitin associated domain (UBA), Winged helix turn helix transcription repressor, HrcA DNA binding, Transcriptional regulator, Serpentine type 7TM GPCR chemoreceptor Srh, Putative Sin3 binding protein, Thiolase, N terminal domain, CpG binding protein zinc finger C terminal domain, PucR C terminal helix turn helix domain, PLU 1 like protein, EVE domain, SPT2 chromatin protein.

[0065] In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of one or multiple DNA binding stretches and one or multiple NLS sequences with or without spacers. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of at least 4 consecutive amino acids of the NLS sequence KQRDAEHRDRTKKKKRSRSRDRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNKVKSRY RSRSRSQSPPKDRKDRDK and at least 4 consecutive amino acids of the DNA binding stretch CSTLNFTLDLSRNNLVTVQPEMFAQLSHLQCLRLSHNCISQAVNGSQFLPLTGLQVLDLSHN KLDLYHEHSFTELPRLEALDLSYNSQPFGMQGVGHNFSFVAHLRTLRHLSLAHNNIHSQVSQ QLCSTSLRALDFSGNALGHMWAEGDLYLH. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of at least 4 consecutive amino acids of the NLS sequence MMPNKVRKIGELVRYLNTNPVGGLLEYARSHGFAAEFKLVDQSGPPHEPKFVYQAKVGGRWF PAVCAHSKKQGKQEAADAALRVLIGENEKAER, at least 4 consecutive amino acids of the DNA binding stretch SGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCI INKVTRNRCQYCRLQKCFEVGMSKEA VRNDRNKKKKEVKEEGSPDSYE, and at least 4 consecutive amino acids of the NLS sequence GRNRAPELGAPGIQKKKR. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of at least 4 consecutive amino acids of the NLS sequence PRRTTRRHPNTQQRASKKKPK, at least 4 consecutive amino acids of the spacer sequence AKKSKTAAKKNDKEAAG, and at least 4 consecutive amino acids of the DNA binding stretch RLAANARERRRMHGLNHAFDQLRNVIPSFNNDKKLSK. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of at least 4 consecutive amino acids of the NLS sequence KRPAATKKAGQAKKK, at least 4 consecutive amino acids of the spacer sequence DEKTEESDTDRLLSSDHEKSHSNLGV, at least 4 consecutive amino acids of the DNA binding stretch RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASR, at least 4 consecutive amino acids of the spacer sequence GGGGSGGGGSGGGGSGGGGS, and at least 4 consecutive amino acids of the NLS sequence KRMNAFMVWAQAARRK. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of up to 3 NLSs optionally interspersed with spacers and up to 3 DNA binding stretches optionally interspersed with spacers, such that the NLSs are comprised of at least 4 consecutive amino acids from each of the following sequences RQARRNRRRRWR, CYGSKNTGAKKRKIDDA, RKHKTNRKPR, spacers which may be comprised of at least 4 consecutive amino acids from each of the following sequences GSAGSAAGSGEF, SDQEAKPSTEDLG, RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNT, and DNA binding sites that are comprised of at least 4 consecutive amino acids from each of the following sequences RKLKNRVAAQTARDRK, KRKRRGNLPKESVKILRDWLYLHRYNAYPSEQEKLSLSGQTNLSVLQICNWFINARRR, AWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTLDPQSEDMFDNGSFLRRRKR. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of up to 3 NLSs optionally interspersed with spacers and up to 3 DNA binding stretches optionally interspersed with spacers, such that the NLSs are comprised of at least 4 consecutive amino acids from each of the following sequences SQKHLQINQTFEELRLVT, RKPVTAQERQREREEKRRRRQERAKEREKRRQERER, KRPMNAFIVWSRDQRRK, spacers which may be comprised of at least 4 consecutive amino acids from each of the following sequences APELLGGP, PVPSTPPTPSPSTPPTPSPSC, AKAEAGAEAGGGAGPGAEDEAGRGAVGDPELGDPPAAPQ, and DNA binding sites that are comprised of at least 4 consecutive amino acids from each of the following sequences PLWRRDGTGHYLCNACGLYHKMNGQNRPLIKPTSCANCQTTTTTLWRRNANGDPVCNACGLY YKLHNINRPLTMKKEGIQTRNRKM, LTTEADSGY, KTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVME YHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPV WIVHGSQ. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of an NLS sequence and a DNA binding stretch from a protein moderately to highly expressed in adipocytes, which contains EYQSAIKVEPASPPYYSEKTQLYNRPHEEPSNSLMAISGFHYGVHACEGCKGFFRRTIRLKL I YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEK. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of an NLS, a DNA binding stretch from a protein moderately to highly expressed in adipocytes, and an NLS, which contains PAAKRVKLDRENHSEIERRRRNKMTAYITELSDMVPTCPDKPAAKRVKLD. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of an NLS, a spacer sequence, and a DNA binding stretch from a protein moderately to highly expressed in adipocytes, which contains

[0066] RRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAEG GGGSGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGE ILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVF QVKTLSLPVWIVHGSQ. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of an NLS, a spacer, a DNA binding stretch from a protein moderately to highly expressed in adipocytes, a spacer, and an NLS, which contains SQKHLQINQTFEELRLVTGGGGSRERNNIAVRKSRGGGGSSQKHLQINQTFEELRLVT. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of 3 NLSs interspersed with spacers, a DNA binding stretch from a protein moderately to highly expressed in adipocytes, and 3 NLSs interspersed with spacers, which contains

[0067] RRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAEG SAGSAAGSGEFPAAKRVKLDGSAGSAAGSGEFSQKHLQINQRFEELRLITKRRHRTTFTSLQ LEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRKSQKHLQINQRFEELRL ITGSAGSAAGSGEFPAAKRVKLDGSAGSAAGSGEFRRTIRLKLI YDRCDLNCRIHKKSRNKC QYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAE. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of 3 NLSs, 3 DNA binding stretches from one or more proteins moderately to highly expressed in adipocytes, and 3 NLSs, all interspersed with spacers, which contains SQKHLQINQTFEELRLVTGGGGSGGGGSGGGGSEYQSAIKVEPASPP YYSEKTQLYNRPHEE PSNSLMAIGGGGSGGGGSGGGGSPAAKRVKLDGGGGSGGGGSGGGGSSGFHYGVHACEGCKG FFRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKGGG GSGGGGSGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNEC SGEILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNE LVFQVKTLSLPVWIVHGSQGGGGSGGGGSGGGGSRERNNIAVRKSRGGGGSGGGGSGGGGS PAAKRVKLDGGGGSGGGGSGGGGSEYQSAIKVEPASPP YYSEKTQLYNRPHEEPSNSLMAIG GGGSGGGGSGGGGSSQKHLQINQTFEELRLVT. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of up to 3 repeats of an NLS-DNA binding stretch unit derived from proteins moderately to highly expressed in adipocytes and connected by flexible spacers, with an amino acid sequence that contains CYGSKNTGAKKRKIDDAKSNPSKRHRDGGGGSGGGGSGGGGSGGGGSCYGSKNTGAKKRKID DAKSNPSKRHRDGGGGSGGGGSGGGGSGGGGSCYGSKNTGAKKRKIDDAKSNPSKRHRD. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of up to 3 different NLS-DNA binding stretch units derived from proteins moderately to highly expressed in adipocytes and connected by flexible spacers, with an amino acid sequence that contains KRMNAFMVWAQAARRKSGFHYGVHACEGCKGFFRRTIRLKLI YDRCDLNCRIHKKSRNKCQY CRFQKCLAVGMSHNAIRFGRMPQAEKEKGGGGSGGGGSGGGGSKRPAATKKAGQAKKKNHNI LERQRRNDLRSSFLTLRDHVPELVKNEKAAKGGGGSGGGGSGGGGSCYGSKNTGAKKRKIDD AKSNPSKRHRD. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of one or multiple DNA binding stretches and one or multiple NLS sequences interspersed with spacers, which is PAAKRVKLDGGGGSPAAKRVKLDGGGGSPAAKRVKLDGGGGSKSNPSKRHRDGGGGSGGGGS KSNPSKRHRDGGGGSGGGGSKSNPSKRHRDGGGGSPAAKRVKLDGGGGSPAAKRVKLDGGGG SPAAKRVKLD. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is KRMNAFMVWAQAARRKAPELLGGPCKRKTTNADRRKAAPELLGGPGRNRAPELGAPGIQKKK RAPELLGGPRLMKNREAARECRGGGGSRRSKNRIAAQRCRKRKGGGGSRREKNKVAAARCRN KKAPELLGGPGRNRAPELGAPGIQKKKRAPELLGGPCKRKTTNADRRKAAPELLGGPKRMNA FMVWAQAARRK. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is SQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRL VTGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEIL NNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQV KTLSLPVWIVHGSQGSAGSAAGSGEFKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQ QAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEK FTVLFESQFSVGSNELVFQVKTLSLPVWIVHGSQGSAGSAAGSGEFKTQTKFAATVRLLVG GKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNM SLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPVWIVHGSQGGGGSSQ KHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVT

[0068] . In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is

[0069] GKKKKGKPGKRREQRKKKRRTGGGGSGGGGSGGGGSGGGGSSGFHYGVHACEGCKGFFRRTI RLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKGGGGSGGGG SGGGGSGGGGSRREKNKVAAARCRNKKGGGGSGGGGSGGGGSGGGGSKRRHRTTFTSLQLEE LEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRK. In one embodiment of any one of the compositions or methods provided herein, the hybrid peptide (e. g., full hybrid peptide) is comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is CYGSKNTGAKKRKIDDAGGGGSGGGGSGGGGSRRERNKIAAAKCRNKKRWPESPKAQASSVP TAQPQAEGSLAKATTAPATTRNTNKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTLDP DSYNMFENGSFLRRRRRGGGGSGGGGSGGGGSKRKKEMANKSAPEAKKKK.

[0070] In one embodiment of any one of the compositions or methods provided herein, the critical pairing number is 1. In one embodiment of any one of the compositions or methods provided herein, the critical pairing number is greater than 1 but less than 8. In one embodiment of any one of the compositions or methods provided herein, the critical pairing number is greater than 1 but less than 37.

[0071] In one embodiment of any one of the compositions or methods provided herein, the peptide comprises CG binding stretches derived at least in part from a Toll-like receptor and combined with at least one amino acid stretch which serves as a nuclear localization sequence. In one embodiment of any one of the compositions or methods provided herein, the peptide comprises at least one DNA binding stretch derived at least in part from a Zinc Finger protein, Homeobox domain, Leucine Rich Domain, Leucine Rich Repeat, basic Helix-Loop-Helix motif, Chromo domain, Chromo-like domain superfamily domain, basic Leucine Zipper domain, or a domain comprised of at least one LXXXXXL motif where L is either a Leucine or Isoleucine, and combined with at least one amino acid stretch which serves as a nuclear localization sequence. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are lipid nanoparticles. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are virus-like particles. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are peptide or polymer carriers. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are lipid nanoparticles with covalently attached targeting moieties. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are lipid nanoparticles with one or more targeting moieties on the surface. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are polymeric nanoparticles. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are nanoparticles comprised of lipid and non-lipid components. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are polymeric nanoparticles comprised of polymer and non-polymer components. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are comprised at least in part of metallic nanoparticles. In one embodiment of any one of the compositions or methods provided herein, the non-viral gene delivery vehicles are physical methods of gene delivery.

[0072] In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise HRACCACGTGGTYD. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TASCACRTGTCW. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GCCAYGYGSS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise MRMGTRHCACGTGDYACKYK. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CACGTGS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CCACSTGWCY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RACCACGTGSTC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KACCACGTGSYY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CASGTGGC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RGCCACGTGCC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GASCACGTGGY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RASCACGTGGT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise SSCCACGTGCYS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CCACGTGC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CCACGTGAA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CGTGG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CACGTGC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CGTGC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GCACGTGCT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise YMCCACGTGYMV. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise SSSCACGYGS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CCACGTGS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise SGCCACGTGGCS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CCACGTGG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GGCACGTGKY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise SCACGTGS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RRMCACGTGR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CCACGTG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise SVRTGASTCAKCM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGACTCAWKSKB. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RTGACTCAD. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGAGTCAK. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGACTCAB. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GRTGACGTCAYC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GRTGAWTCAYC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AATGAYRCG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RATGAYRCG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KATGASTCAYM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise DRTGACTCATY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RRTGASTCAKS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KKRTGACTCATMM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise DRATGACTCATHY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise ATGACTCAT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RTGACTCAT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise YKRTGACTMATMC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RRTGACTMAT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RTGACGYMAY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGASTCAYCH. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RTGACTCAYYC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KRRTGASTCAB. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GRTGACGTMAT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RRTGASTCAB. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RTGAGTCAY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RTGACGTMAT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RTGASTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KRTGASTCAY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KRTGACGTCAYM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KKRTKACGTCAYCGC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KKRTGAGTCAYM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KRTGASTCAYMV. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KKRTGAGTCAYMV. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RTGAGTCAYM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise DRTGACGTCATMMKTY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGAMTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGACTCAK. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KKWATGASKCATMY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RTGAGTCAYCS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise DVTGASTCATB. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise BGATGACGTCATCR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGASTCAT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GATGACGTCATCR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GATGACGTCAYC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GATGAYGTCATC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AGTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGACTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RSTGACTCMGW. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise ACSMGGAAGTR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RASRMGGAAGTR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GAMCCGGAAGTR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AACRAGGAAGTR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AASRAGGAAGTR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise WAYWTCCKK. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise YYWRRGGTCAAAGGTCAHVBD. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AASTRGGTCACSGTGACCYACWT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise WASYRGGKCAAAGKTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise WGAMCTTTGACCY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AGGTCAG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AWSTRGGKCAAAGGKCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise YYWRRGGTCAAAGGTCAYMK. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise STRGGTCACSGTGACCYACW. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TRGGTCACSGTGACCYACW. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AWSTRGGTYAST. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise MRRGGKYAAWRGGTCAC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AANNNAGGTCANNGGNCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AANNAGGTNANNGGTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AAANNAGGTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGNCNNNTGACCTNNNTT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGACCTNNNTT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise ARRGGTCAAAGGTCAH. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RRGGTCAAAGGTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CWRAWCYAGGYCAWAGKTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise YMRGGTCATWGGGGTSARG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TGACCTY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RGGTCARAGGTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AWGTRGGTCAAAGGTCAT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AWGTRGGTCAAAGGTCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise ARRGGTCRTGACCYYT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise DGRGGTCAAAGGTCRY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise ARRGGTCGYGACCYYK. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise MSTGWCCTB. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RGGTCAR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AAAAGGTCAM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RAGGTC AAAAGGTCAM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RAGGTCRTGACCTY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AAAAGGTCAH. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RAGGTCAAAAGGTCAH. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RAGGTCRTGACCT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CCAGGTGG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GCCACCTGSCTGYD. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CCACCTGCMN. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise DRCAGGTGYR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RCAGGTG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise ARCAGGTGCA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RRCAGGTGYR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RRCAGGTGCR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise YCAGGTG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KCACCTGM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise SSSRSCKCACCTGS. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CACCTGSRK. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RRCAGGTGY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise AYGCACCTGTMRY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GCACCTGT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise WWWMRAKRCACCTGYTAKWHAW. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTCCCRKAA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise DAWTTCYWGGAAWYH. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTCCCRGAAWTBSKWTWCCKRGRR. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise YAWTTCYW. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise SWYTTCYW. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KRYWYTTCYKRGA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RSWTTTCTARGAA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTCYYRGAAAY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTTCYKRGAAW. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise KAWTTCYTGGAAWTY. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise RAWTTCCARGAAWTM. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTTCYKRGAAA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTCYYAGGAAWYT. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTCCNGGAA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTCCTGGAA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise CCNNGGAANNNNNA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTCC. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise GGAANNNNNA. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise TTCNNGG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise at least two of the following sequences HRACCACGTGGTYD, TASCACRTGTCW, GCCAYGYGSS, MRMGTRHCACGTGDYACKYK, CACGTGS, CCACSTGWCY, RACCACGTGSTC, KACCACGTGSYY, CASGTGGC, RGCCACGTGCC, GASCACGTGGY, RASCACGTGGT, SSCCACGTGCYS, CCACGTGC, CCACGTGAA, CGTGG, CACGTGC, CGTGC, GCACGTGCT, YMCCACGTGYMV, SSSCACGYGS, CCACGTGS, SGCCACGTGGCS, CCACGTGG, GGCACGTGKY, SCACGTGS, RRMCACGTGR, CCACGTG, SVRTGASTCAKCM, GACTCAWKSKB, TGACTCAD, TGAGTCAK, TGACTCAB, GRTGACGTCAYC, GRTGAWTCAYC, ATGAYRCG, ATGAYRCG, KATGASTCAYM, DRTGACTCATY, RRTGASTCAKS, KKRTGACTCATMM, DRATGACTCATHY, ATGACTCAT, RTGACTCAT, YKRTGACTMATMC, RRTGACTMAT, RTGACGYMAY, TGASTCAYCH, RTGACTCAYYC, KRRTGASTCAB, GRTGACGTMAT, RRTGASTCAB, RTGAGTCAY, RTGACGTMAT, RTGASTCA, KRTGASTCAY, KRTGACGTCAYM, KKRTKACGTCAYCGC, KKRTGAGTCAYM, KRTGASTCAYMV, KKRTGAGTCAYMV, RTGAGTCAYM, DRTGACGTCATMMKTY, TGAMTCA, TGACTCAK, KKWATGASKCATMY, RTGAGTCAYCS, DVTGASTCATB, BGATGACGTCATCR, TGASTCAT, ATGACGTCATCR, ATGACGTCAYC, GATGAYGTCATC, AGTCA, TGACTCA, RSTGACTCMGW, ACSMGGAAGTR, RASRMGGAAGTR, GAMCCGGAAGTR, AACRAGGAAGTR, ASRAGGAAGTR, AYWTCCKK, YYWRRGGTCAAAGGTCAHVBD, AASTRGGTCACSGTGACCYACWT, WASYRGGKCAAAGKTCA, WGAMCTTTGACCY, AGGTCAG, AWSTRGGKCAAAGGKCA, YYWRRGGTCAAAGGTCAYMK, STRGGTCACSGTGACCYACW, TRGGTCACSGTGACCYACW, AWSTRGGTYAST, MRRGGKYAAWRGGTCAC, AANNNAGGTCANNGGNCA, AANNAGGTNANNGGTCA, AAANNAGGTCA, TGNCNNNTGACCTNNNTT, TGACCTNNNTT, ARRGGTCAAAGGTCAH, RRGGTCAAAGGTCA, CWRAWCYAGGYCAWAGKTCA, YMRGGTCATWGGGGTSARG, TGACCTY, RGGTCARAGGTCA, AWGTRGGTCAAAGGTCAT, AWGTRGGTCAAAGGTCA, ARRGGTCRTGACCYYT, DGRGGTCAAAGGTCRY, ARRGGTCGYGACCYYK, MSTGWCCTB, RGGTCAR, AAAAGGTCAM, RAGGTCAAAAGGTCAM, RAGGTCRTGACCTY, AAAAGGTCAH, RAGGTCAAAAGGTCAH, RAGGTCRTGACCT, CCAGGTGG, GCCACCTGSCTGYD, CCACCTGCMN, DRCAGGTGYR, RCAGGTG, ARCAGGTGCA, RRCAGGTGYR, RRCAGGTGCR, YCAGGTG, KCACCTGM, SSSRSCKCACCTGS, CACCTGSRK, RRCAGGTGY, AYGCACCTGTMRY, GCACCTGT, WWWMRAKRCACCTGYTAKWHAW, TTCCCRKAA, DAWTTCYWGGAAWYH, TTCCCRGAAWTBSKWTWCCKRGRR, YAWTTCYW, SWYTTCYW, KRYWYTTCYKRGA, RSWTTTCTARGAA, TTCYYRGAAAY, TTTCYKRGAAW, KAWTTCYTGGAAWTY, RAWTTCCARGAAWTM, TTTCYKRGAAA, TTCYYAGGAAWYT, TTCCNGGAA, TTCCTGGAA, CCNNGGAANNNNNA, TTCC, GGAANNNNNA, TTCNNGG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) comprise at least 80% of at least one of the following sequences HRACCACGTGGTYD, TASCACRTGTCW, GCCAYGYGSS, MRMGTRHCACGTGDYACKYK, CACGTGS, CCACSTGWCY, RACCACGTGSTC, KACCACGTGSYY, CASGTGGC, RGCCACGTGCC, GASCACGTGGY, RASCACGTGGT, SSCCACGTGCYS, CCACGTGC, CCACGTGAA, CGTGG, CACGTGC, CGTGC, GCACGTGCT, YMCCACGTGYMV, SSSCACGYGS, CCACGTGS, SGCCACGTGGCS, CCACGTGG, GGCACGTGKY, SCACGTGS, RRMCACGTGR, CCACGTG, SVRTGASTCAKCM, GACTCAWKSKB, TGACTCAD, TGAGTCAK, TGACTCAB, GRTGACGTCAYC, GRTGAWTCAYC, ATGAYRCG, ATGAYRCG, KATGASTCAYM, DRTGACTCATY, RRTGASTCAKS, KKRTGACTCATMM, DRATGACTCATHY, ATGACTCAT, RTGACTCAT, YKRTGACTMATMC, RRTGACTMAT, RTGACGYMAY, TGASTCAYCH, RTGACTCAYYC, KRRTGASTCAB, GRTGACGTMAT, RRTGASTCAB, RTGAGTCAY, RTGACGTMAT, RTGASTCA, KRTGASTCAY, KRTGACGTCAYM, KKRTKACGTCAYCGC, KKRTGAGTCAYM, KRTGASTCAYMV, KKRTGAGTCAYMV, RTGAGTCAYM, DRTGACGTCATMMKTY, TGAMTCA, TGACTCAK, KKWATGASKCATMY, RTGAGTCAYCS, DVTGASTCATB, BGATGACGTCATCR, TGASTCAT, ATGACGTCATCR, ATGACGTCAYC, GATGAYGTCATC, AGTCA, TGACTCA, RSTGACTCMGW, ACSMGGAAGTR, RASRMGGAAGTR, GAMCCGGAAGTR, AACRAGGAAGTR, ASRAGGAAGTR, AYWTCCKK, YYWRRGGTCAAAGGTCAHVBD, AASTRGGTCACSGTGACCYACWT, WASYRGGKCAAAGKTCA, WGAMCTTTGACCY, AGGTCAG, AWSTRGGKCAAAGGKCA, YYWRRGGTCAAAGGTCAYMK, STRGGTCACSGTGACCYACW, TRGGTCACSGTGACCYACW, AWSTRGGTYAST, MRRGGKYAAWRGGTCAC, AANNNAGGTCANNGGNCA, AANNAGGTNANNGGTCA, AAANNAGGTCA, TGNCNNNTGACCTNNNTT, TGACCTNNNTT, ARRGGTCAAAGGTCAH, RRGGTCAAAGGTCA, CWRAWCYAGGYCAWAGKTCA, YMRGGTCATWGGGGTSARG, TGACCTY, RGGTCARAGGTCA, AWGTRGGTCAAAGGTCAT, AWGTRGGTCAAAGGTCA, ARRGGTCRTGACCYYT, DGRGGTCAAAGGTCRY, ARRGGTCGYGACCYYK, MSTGWCCTB, RGGTCAR, AAAAGGTCAM, RAGGTCAAAAGGTCAM, RAGGTCRTGACCTY, AAAAGGTCAH, RAGGTCAAAAGGTCAH, RAGGTCRTGACCT, CCAGGTGG, GCCACCTGSCTGYD, CCACCTGCMN, DRCAGGTGYR, RCAGGTG, ARCAGGTGCA, RRCAGGTGYR, RRCAGGTGCR, YCAGGTG, KCACCTGM, SSSRSCKCACCTGS, CACCTGSRK, RRCAGGTGY, AYGCACCTGTMRY, GCACCTGT, WWWMRAKRCACCTGYTAKWHAW, TTCCCRKAA, DAWTTCYWGGAAWYH, TTCCCRGAAWTBSKWTWCCKRGRR, YAWTTCYW, SWYTTCYW, KRYWYTTCYKRGA, RSWTTTCTARGAA, TTCYYRGAAAY, TTTCYKRGAAW, KAWTTCYTGGAAWTY, RAWTTCCARGAAWTM, TTTCYKRGAAA, TTCYYAGGAAWYT, TTCCNGGAA, TTCCTGGAA, CCNNGGAANNNNNA, TTCC, GGAANNNNNA, TTCNNGG. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) is / are comprised of at least two of the following sequences, HRACCACGTGGTYD, TASCACRTGTCW, GCCAYGYGSS, MRMGTRHCACGTGDYACKYK, CACGTGS, CCACSTGWCY, RACCACGTGSTC, KACCACGTGSYY, CASGTGGC, RGCCACGTGCC, GASCACGTGGY, RASCACGTGGT, SSCCACGTGCYS, CCACGTGC, CCACGTGAA, CGTGG, CACGTGC, CGTGC, GCACGTGCT, YMCCACGTGYMV, SSSCACGYGS, CCACGTGS, SGCCACGTGGCS, CCACGTGG, GGCACGTGKY, SCACGTGS, RRMCACGTGR, CCACGTG, SVRTGASTCAKCM, GACTCAWKSKB, TGACTCAD, TGAGTCAK, TGACTCAB, GRTGACGTCAYC, GRTGAWTCAYC, ATGAYRCG, ATGAYRCG, KATGASTCAYM, DRTGACTCATY, RRTGASTCAKS, KKRTGACTCATMM, DRATGACTCATHY, ATGACTCAT, RTGACTCAT, YKRTGACTMATMC, RRTGACTMAT, RTGACGYMAY, TGASTCAYCH, RTGACTCAYYC, KRRTGASTCAB, GRTGACGTMAT, RRTGASTCAB, RTGAGTCAY, RTGACGTMAT, RTGASTCA, KRTGASTCAY, KRTGACGTCAYM, KKRTKACGTCAYCGC, KKRTGAGTCAYM, KRTGASTCAYMV, KKRTGAGTCAYMV, RTGAGTCAYM, DRTGACGTCATMMKTY, TGAMTCA, TGACTCAK, KKWATGASKCATMY, RTGAGTCAYCS, DVTGASTCATB, BGATGACGTCATCR, TGASTCAT, ATGACGTCATCR, ATGACGTCAYC, GATGAYGTCATC, AGTCA, TGACTCA, RSTGACTCMGW, ACSMGGAAGTR, RASRMGGAAGTR, GAMCCGGAAGTR, AACRAGGAAGTR, ASRAGGAAGTR, AYWTCCKK, YYWRRGGTCAAAGGTCAHVBD, AASTRGGTCACSGTGACCYACWT, WASYRGGKCAAAGKTCA, WGAMCTTTGACCY, AGGTCAG, AWSTRGGKCAAAGGKCA, YYWRRGGTCAAAGGTCAYMK, STRGGTCACSGTGACCYACW, TRGGTCACSGTGACCYACW, AWSTRGGTYAST, MRRGGKYAAWRGGTCAC, AANNNAGGTCANNGGNCA, AANNAGGTNANNGGTCA, AAANNAGGTCA, TGNCNNNTGACCTNNNTT, TGACCTNNNTT, ARRGGTCAAAGGTCAH, RRGGTCAAAGGTCA, CWRAWCYAGGYCAWAGKTCA, YMRGGTCATWGGGGTSARG, TGACCTY, RGGTCARAGGTCA, AWGTRGGTCAAAGGTCAT, AWGTRGGTCAAAGGTCA, ARRGGTCRTGACCYYT, DGRGGTCAAAGGTCRY, ARRGGTCGYGACCYYK, MSTGWCCTB, RGGTCAR, AAAAGGTCAM, RAGGTC AAAAGGTCAM, RAGGTCRTGACCTY, AAAAGGTCAH, RAGGTCAAAAGGTCAH, RAGGTCRTGACCT, CCAGGTGG, GCCACCTGSCTGYD, CCACCTGCMN, DRCAGGTGYR, RCAGGTG, ARCAGGTGCA, RRCAGGTGYR, RRCAGGTGCR, YCAGGTG, KCACCTGM, SSSRSCKCACCTGS, CACCTGSRK, RRCAGGTGY, AYGCACCTGTMRY, GCACCTGT, WWWMRAKRCACCTGYTAKWHAW, TTCCCRKAA, DAWTTCYWGGAAWYH, TTCCCRGAAWTBSKWTWCCKRGRR, YAWTTCYW, SWYTTCYW, KRYWYTTCYKRGA, RSWTTTCTARGAA, TTCYYRGAAAY, TTTCYKRGAAW, KAWTTCYTGGAAWTY, RAWTTCCARGAAWTM, TTTCYKRGAAA, TTCYYAGGAAWYT, TTCCNGGAA, TTCCTGGAA, CCNNGGAANNNNNA, TTCC, GGAANNNNNA, TTCNNGG, where one is added before the promoter driving expression of the therapeutic gene and another is added after the PolyA signal of the therapeutic gene. In one embodiment of any one of the compositions or methods provided herein, the DNA sequence (s) is / are comprised of at least two of the following sequences, HRACCACGTGGTYD, TASCACRTGTCW, GCCAYGYGSS, MRMGTRHCACGTGDYACKYK, CACGTGS, CCACSTGWCY, RACCACGTGSTC, KACCACGTGSYY, CASGTGGC, RGCCACGTGCC, GASCACGTGGY, RASCACGTGGT, SSCCACGTGCYS, CCACGTGC, CCACGTGAA, CGTGG, CACGTGC, CGTGC, GCACGTGCT, YMCCACGTGYMV, SSSCACGYGS, CCACGTGS, SGCCACGTGGCS, CCACGTGG, GGCACGTGKY, SCACGTGS, RRMCACGTGR, CCACGTG, SVRTGASTCAKCM, GACTCAWKSKB, TGACTCAD, TGAGTCAK, TGACTCAB, GRTGACGTCAYC, GRTGAWTCAYC, ATGAYRCG, ATGAYRCG, KATGASTCAYM, DRTGACTCATY, RRTGASTCAKS, KKRTGACTCATMM, DRATGACTCATHY, ATGACTCAT, RTGACTCAT, YKRTGACTMATMC, RRTGACTMAT, RTGACGYMAY, TGASTCAYCH, RTGACTCAYYC, KRRTGASTCAB, GRTGACGTMAT, RRTGASTCAB, RTGAGTCAY, RTGACGTMAT, RTGASTCA, KRTGASTCAY, KRTGACGTCAYM, KKRTKACGTCAYCGC, KKRTGAGTCAYM, KRTGASTCAYMV, KKRTGAGTCAYMV, RTGAGTCAYM, DRTGACGTCATMMKTY, TGAMTCA, TGACTCAK, KKWATGASKCATMY, RTGAGTCAYCS, DVTGASTCATB, BGATGACGTCATCR, TGASTCAT, ATGACGTCATCR, ATGACGTCAYC, GATGAYGTCATC, AGTCA, TGACTCA, RSTGACTCMGW, ACSMGGAAGTR, RASRMGGAAGTR, GAMCCGGAAGTR, AACRAGGAAGTR, ASRAGGAAGTR, AYWTCCKK, YYWRRGGTCAAAGGTCAHVBD, AASTRGGTCACSGTGACCYACWT, WASYRGGKCAAAGKTCA, WGAMCTTTGACCY, AGGTCAG, AWSTRGGKCAAAGGKCA, YYWRRGGTCAAAGGTCAYMK, STRGGTCACSGTGACCYACW, TRGGTCACSGTGACCYACW, AWSTRGGTYAST, MRRGGKYAAWRGGTCAC, AANNNAGGTCANNGGNCA, AANNAGGTNANNGGTCA, AAANNAGGTCA, TGNCNNNTGACCTNNNTT, TGACCTNNNTT, ARRGGTCAAAGGTCAH, RRGGTCAAAGGTCA, CWRAWCYAGGYCAWAGKTCA, YMRGGTCATWGGGGTSARG, TGACCTY, RGGTCARAGGTCA, AWGTRGGTCAAAGGTCAT, AWGTRGGTCAAAGGTCA, ARRGGTCRTGACCYYT, DGRGGTCAAAGGTCRY, ARRGGTCGYGACCYYK, MSTGWCCTB, RGGTCAR, AAAAGGTCAM, RAGGTC AAAAGGTCAM, RAGGTCRTGACCTY, AAAAGGTCAH, RAGGTCAAAAGGTCAH, RAGGTCRTGACCT, CCAGGTGG, GCCACCTGSCTGYD, CCACCTGCMN, DRCAGGTGYR, RCAGGTG, ARCAGGTGCA, RRCAGGTGYR, RRCAGGTGCR, YCAGGTG, KCACCTGM, SSSRSCKCACCTGS, CACCTGSRK, RRCAGGTGY, AYGCACCTGTMRY, GCACCTGT, WWWMRAKRCACCTGYTAKWHAW, TTCCCRKAA, DAWTTCYWGGAAWYH, TTCCCRGAAWTBSKWTWCCKRGRR, YAWTTCYW, SWYTTCYW, KRYWYTTCYKRGA, RSWTTTCTARGAA, TTCYYRGAAAY, TTTCYKRGAAW, KAWTTCYTGGAAWTY, RAWTTCCARGAAWTM, TTTCYKRGAAA, TTCYYAGGAAWYT, TTCCNGGAA, TTCCTGGAA, CCNNGGAANNNNNA, TTCC, GGAANNNNNA, TTCNNGG, which are separated by at least 6 nucleotides.

[0073] In one embodiment of any one of the compositions or methods provided herein, the DNA is linear double stranded DNA. In one embodiment of any one of the compositions or methods provided herein, the DNA is linear single stranded DNA. In one embodiment of any one of the compositions or methods provided herein, the DNA is circular double stranded DNA. In one embodiment of any one of the compositions or methods provided herein, the DNA is circular single stranded DNA. In one embodiment of any one of the compositions or methods provided herein, the DNA is partially double stranded DNA. In one embodiment of any one of the compositions or methods provided herein, the DNA is a DNA-RNA hybrid. In one embodiment of any one of the compositions or methods provided herein, the DNA is a DNA-peptide hybrid. In one embodiment of any one of the compositions or methods provided herein, the DNA is a synthetically modified DNA or DNA hybrid. In one embodiment of any one of the compositions or methods provided herein, the DNA is comprised of chemically modified and unmodified DNA.

[0074] In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for human pathologies. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for animal pathologies. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for mammalian pathologies. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for augmentation of gene expression, which is reduced as a function of aging. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for the replacing of missing or nonfunctioning genes. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for the alleviation of pathologies caused by metabolic diseases. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for the alleviation of pathologies caused by musculoskeletal diseases. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for the alleviation of pathologies caused by cardiovascular diseases. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for the alleviation of pathologies caused by diseases of the central and / or peripheral nervous systems. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for the alleviation of pathologies in autoimmune diseases. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for the alleviation of pathologies caused by infectious diseases. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for the alleviation of pathologies caused by environmental conditions. In one embodiment of any one of the compositions or methods provided herein, the composition or method is intended for genome modification, silencing, or otherwise altering the genome or level of expression.

[0075] In an aspect is a method of administering any one of the compositions provided herein to a subject in need thereof, such as for any one of the purposes provided herein.

[0076] In an aspect is any one of the constructs provided herein, such as in the Examples. In an aspect is a composition comprising any one of the constructs provided herein, such as in the Examples.

[0077] BRIEF DESCRIPTION OF THE FIGURES FIG. 1 illustrates an exemplary construct from Example 1.

[0078] FIG. 2 illustrates an exemplary construct from Example 3.

[0079] FIG. 3 illustrates an exemplary construct from Example 4.

[0080] FIG. 4 illustrates an exemplary construct from Example 5.

[0081] FIG. 5 illustrates an exemplary construct from Example 6.

[0082] DETAILED DESCRIPTION OF THE INVENTION

[0083] Before describing the present invention in detail, it is to be understood that this invention is not limited to particularly exemplified materials or process parameters as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments of the invention only, and is not intended to be limiting of the use of alternative terminology to describe the present invention.

[0084] All publications, patents and patent applications cited herein, whether supra or infra, are hereby incorporated by reference in their entirety for all purposes. Such incorporation by reference is not intended to be an admission that any of the incorporated publications, patents and patent applications cited herein constitute prior art.

[0085] As used in this specification and the appended claims, the singular forms "a, " "an" and "the" include plural referents unless the content clearly dictates otherwise. For example, reference to "a molecule" includes a mixture of two or more such molecules or a plurality of such molecules, and the like.

[0086] As used herein, the term "comprise" or variations thereof such as "comprises" or "comprising" are to be read to indicate the inclusion of any recited integer (e. g. a feature, element, characteristic, property, method / process step or limitation) or group of integers (e. g. features, elements, characteristics, properties, method / process steps or limitations) but not the exclusion of any other integer or group of integers. Thus, as used herein, the term "comprising" is inclusive and does not exclude additional, unrecited integers or method / process steps. In embodiments of any of the compositions and methods provided herein, "comprising" may be replaced with "consisting essentially of" or "consisting of". The phrase "consisting essentially of" is used herein to require the specified integer (s) or steps as well as those which do not materially affect the character or function of the claimed invention. As used herein, the term "consisting" is used to indicate the presence of the recited integer (e. g. a feature, element, characteristic, property, method / process step or limitation) or group of integers (e. g. features, elements, characteristics, properties, method / process steps or limitations) alone.

[0087] The present invention generally discloses means of enhancing DNA transport to the nucleus of a cell for use with non-viral gene therapy vectors or viral gene therapy vectors that require augmentation of DNA transport from the cytoplasm to the nucleus. In general, the present invention discloses a strategy for augmenting or enhancing nuclear transport of cytoplasmic DNA by combining within a non-viral gene delivery system several elements to facilitate said transport. Some such elements include the therapeutic DNA cassette, which can be single- or double-stranded, circular or linear, and with and without chemical modifications. Said cassette may be a DNA-peptide or DNA-RNA hybrid but should include at least one and preferably in some embodiments a plethora of protein-binding sites, or DNA protein-binding sequences or protein-binding stretches, which are used to non-covalently anchor the DNA for transport. Said protein-binding stretches or DNA protein-binding sequences are sequences of DNA that are inserted to provide binding sites for peptides or proteins co-f ormulated with the non-viral vector or viral vector gene therapy. The therapeutic DNA cassette may have therapeutic coding regions and / or therapeutic non-coding regions or may augment genes, replace genes, or deliver therapeutic noncoding DNA. In addition, the disclosed composition can generally include one or more non-covalently attached peptides, proteins, or protein fragments, which are comprised of at least one nuclear localization sequence, at least one DNA binding stretch of amino acids or sequence of amino acids, which binds to one or more of the protein-binding stretches from the said DNA cassette, and optionally at least one spacer, for the purposes provided herein - the hybrid peptide or hybrid peptide or fusion peptide. The nuclear localization sequence (NLS) is intended to bind and transport proteins that carry the DNA and peptide to the nucleus and can be derived from natural or synthetic nuclear localization sequences, preferably in some embodiments from nuclear localization sequences that are known to function in the cell type where the genetic cargo is being delivered or is predominantly targeting. The spacer is a stretch of amino acids, or an amino acid, or a peptide bond that provides sufficient distance between the nuclear localization sequence of amino acids and the DNA binding stretch of amino acids, such that the nuclear localization stretch can be readily bound by proteins capable of transporting the peptide and DNA to the nucleus and the DNA binding stretch can readily bind the DNA protein binding site.

[0088] For optimal functionality the DNA cassette and peptide can be formulated in a stoichiometric ratio equal to or approximately equal to a critical pairing number. Said critical pairing number can be defined as the number of DNA binding peptides divided by the average valence of the therapeutic cassettes used in the treatment for a given partner pair and should preferably exceed 1.0, and most preferably 1.1, but be lower than 6.0 and preferably lower than 3.4, in some embodiments. In some embodiments of the present invention the critical pairing number is between 0.8 and 2.2. In other embodiments of the present invention the critical pairing number is between 2.2 and 3.4. In yet other embodiments of the present invention the critical pairing number is between 2.2 and 4.6. And in yet other embodiments of the present invention the critical pairing number is between 2.2 and 6.0. The NLS is a stretch of at least 4 and no more than 40 amino acids and is intended to bind to NLS binding proteins to enable transport of the peptide and DNA to the nucleus. The NLS sequence can contain more than one binding site for the NLS binding proteins. Alternatively, multiple NLS sequences can be used, which can be separated by flexible, or semi-flexible peptide spacers. The NLS sequence can be comprised of sequences containing DEXX motifs such as DEAH, DEAD, DECH, sequences containing LXXLL motifs such as LHTLL, LHKLL, or LRYLL, or a number of motifs with stretches of basic amino acids. Some specific examples of NLS sequences that can be used to achieve the functionality disclosed in the present invention include KRFARADKRGKLPR, KIEPSKPTATRKRRWSAPETRKLEKSEDEPPLTLPKPSL, PKGRQRK, and KPRRIRKPR.

[0089] In general, an NLS sequence can be derived from any of the NLS sequences in the table below (Table 1), or functional fragments or combinations of one or more functional fragments or full sequences in the table below (Table 1), with the term functional defined as enabling nuclear translocation directly or by binding to proteins or other intracellular components that enable nuclear translocation.

[0090] Table 1

[0091]

[0092]

[0093]

[0094]

[0095]

[0096]

[0097]

[0098]

[0099]

[0100]

[0101]

[0102] The NLS sequence may be used on its own when coupling with the DNA binding amino acid sequence or may be separated by one or more stretches of amino acids or non-amino acid chemical moieties. Optionally, the NLS sequence may be added to either side of the DNA binding amino acid sequence or sequences or several NLS sequences may be added to the construct on one or either side of the DNA binding sequence or sequences. The one or more NLS sequences and the one or more DNA binding sequences may be separated by one or more amino acid spacers, that are rigid, semi-rigid, or flexible, but most ideally flexible and sufficiently long to facilitate binding, or at least not sterically inhibit binding, of DNA by the DNA binding amino acid sequence or sequences and facilitate binding of the NLS by the factors enabling nuclear transport. To facilitate said, the NLS sequence can be separated from the DNA binding peptide by a spacer. The spacer can be as short as a peptide bond or as long as 40 amino acids, but preferably may be between 6 and 32 amino acids and may be comprised of at least a part of at least one of the spacers in the following table (Table 2), but optionally at least a part of several spacers or several parts of spacers from the following table (Table 1).

[0103] Table 2

[0104]

[0105]

[0106]

[0107]

[0108] Alternatively the spacer sequence may be derived from proteins with high disorder propensity, or predominantly from proteins with high disorder propensity, such that at least half of the amino acids in a spacer sequence are derived from amino acids with disorder propensity of 0.4 or greater, but most ideally at least half of the amino acids in the spacer sequence are derived from amino acids with disorder propensity of 0.43 or greater.

[0109] Table 3

[0110]

[0111]

[0112]

[0113] Several spacers can be utilized in tandem, spacers can be added to either side of the NLS signal or either side of the DNA binding peptide, and can be optionally added between the different DNA binding peptides and different NLS signals if multiple DNA binding sites or NLS signals are used in the hybrid peptide.

[0114] Finally, the hybrid peptide must contain at least one DNA binding stretch or at least one DNA binding peptide within the overall hybrid peptide, in some embodiments. The DNA binding stretch can be derived at least in part from at least a part of the peptides in the following table (Table 4). Optionally, the DNA binding stretch of amino acids can be derived from a combination of one or more sequences containing at least one stretch of at least 4 amino acids derived from the table below (Table 4), and most preferably at least one contiguous stretch from at least one of the sequences below, in some embodiments. DNA binding stretches can be added directly one after another or separated by previously discussed spacers and may optionally be flanked or flank NLS amino acid sequences, which can be optionally also separated from the DNA binding stretches by spacers.

[0115] Table 4

[0116]

[0117]

[0118]

[0119]

[0120]

[0121]

[0122]

[0123] Most preferably, in some embodiments, the DNA binding peptide or binding stretch is derived from a group of DNA binding peptides that are expressed in a cell predominantly targeted or targeted by the therapeutic gene therapy or the gene therapy vector, or a cell which is the main eventual target of the therapeutic gene therapy. As an example, gene therapy constructs, which target adipocytes may benefit from the selection of DNA binding peptides from proteins such as TBX18, MESP1, HOXC9, PPAR-gamma, GSC, EN1, CEBPA, BNC1, STAT5A, SNAI1, FOSL1, or Myc. In a more specific example the DNA binding peptide can be derived from one or more of the DNA binding stretches of amino acids from one or more of the following sequences: eenvkRrTHNvLErqRRnelkr,

[0124] eenvkRrTHNvLERqRRNelkRsf f alrdqipelennekapKvvilk, mnvkRrtHNvLERqRRNelkRsff alrdqipelennekapKvvilk, hmnvkRrtHNvLERqRRNelkRsff alrdqipelennekapKvvilk, serrrNHNiLErqRRndlRssf It IrdhvpelvknekaaKvvilk, tkkkyHSyLErkRRndqRsrf lalrdevpalascsrVsKvmilv, saadkRaHHNaLErkRRdhiKdsfhslrdsvpslqgekasRaqild, errrvRRerNKlAAakCRnrrkeltdf IqaetdkledeksglqreiEelqkq, ekrriRRerNKlAAakCRnrRrelte, ekrriRRerNKmAAakCRnrRreltd, krriRRerNKmAAakSRnrrre,

[0125] cgdkaSGf HYgvhacEGcKGf fRRtirlkliydrcdlncrihkksrNkcqyc, cgdkaSGf HYgvhacEGcKGf fRRtirmkleyekcersckiqkknrNkcqyc, cgdkaSGy HYgvhacEGcKGf fRRtirlklvydkcdrsckiqkknrNkcqyc, scgslNmecrvcgdKaSGFHYgvhacEGcKGf fRRtirmkleyekcersckiqkknrNkcqy c,

[0126] qarkaFnckycnkeyLSLGAlKMhlRshtlp, cnktySTf SGlaKhkqLhcdaq, ppqvlKtqtkf aatvrllvggklnvhmnppqvkatiiseqqaksllknentrnecsgeilnn cc,

[0127] meyhqatgtlsahf rnmslkrikradrrgaEsvteekftvlf esqf svgsnelvf qvktlsl p, vvviVHGSQdhnat, ppqvlKtqtkfaatvrllvggklnvhmnppqvkatiiseqqaksllknentrndysgei Inn cc,

[0128] meyhqatgtlsahf rnmsl krikrsdrrgaEsvt eekf til f esqf svggnelvf qvktlsl pvvviVHGSQdnnat,

[0129] ppqvlKtqtkf qagvr fl Iglrf Igapakppl vradmvtekqarels vpqgpgagae st gei in,

[0130] tvplensipgnccsalf knlllkkikrcerkgtEsvteekcavlf sasftlgpgklpiqlqa 1, slplvviVHGNQdnnak, ppqvlKtqtkf qagvr fl Iglrf Ipakpplvradmvt ekqarele st gei innt vplens ip gn,

[0131] csalf knlllkkikrcerkgtEsvteekcavlf sas ft IgpgklpiqlqalslplvviVHGN Qdnnak,

[0132] ppqvlKtqtkf qagvr fl Iglrf pakpplvradmvt ekqarele st gei innt vplens ipg nc,

[0133] salf knlllkkikrcEgtesvteekcavlf sasftlgpgklpiqlqalslplvviVHGNQdn nak, ppqvlKtqtkf qagvrf llglrf Igpakpplvradmvt ekqaretgei innt vplensipgn cc,

[0134] salf knlllkkikrcerkgtEsvteekcavlf sas ft IglpiqlqalslplvviVHGNQdnn ak,

[0135] ppqvlKtqtkf qagvrf llglrf Igapakpplvradmvtekqaretgei innt vplensipg nc,

[0136] salf knlllkkikrcerkgtEsvteekcavlf sas ft IgppiqlqalslplvviVHGNQdnn ak,

[0137] ppqvlKtqtkf qagvrf llglrf Igapakpplvradmvtekqaretgei innt vplensipg nc,

[0138] csalf knlllkkikrcEgtesvteekcavlf sasftlgpiqlqalslplvviVHGNQdnnak r

[0139] ItkteHpkSsf rlhRMrrMgsasr, chkmySNKGTIRVhyktv, neyrvRRerNNiAVrkSRdkakq, leyrlRReRNNiAVrKSRdkakr, eyrlrRerNNiAVrkSRdkakr, eykirRerNNiAVrkSRdkakm, ssgprTrklkk, kpkkkNpnkeDKRPRtaftaeqlqrlkaef qtnrylteqrrqslaqelslneSQiKIwfQNk rAKikKatgnk,

[0140] dldrpKRTRt sftaeqlyrlemef qrcqyvvgrertelarqlnlseTQvKVWfQNRrTKqkK dqgkd,

[0141] dldrpKRTRt sftaeqlyrlemef qrcqyvvgre rtel ar qlnlseTQvKVwfQNrrTKqkK dqsrd,

[0142] IhcrrKRRHRtiftdeqlealenlf qetkypdvgtreqlarkvhlreEKvEVwfKNrrAKwr Rqkrss,

[0143] pgsqrRtRRHRtif seeqlqalealfvqnqypdvstrerlagrirlreERvEVwfKNrrAKw rHqkras,

[0144] harstRKKRcpytkyqtlelekef If nmyltrdrryevarvlnlteRQvKIwfQNrrMKmkK mnkek,

[0145] harssRKKRcpytkyqtlelekef If nmyltrdrrhevarllnlseRQvKIwfQNrrMKMkK mnkeq,

[0146] harstRKKRcpytkhqtlelekef If nmyltrdrryevarllnlteRQvKIwfQNrrMKMkK inkdr,

[0147] harssRKKRcpytkyqtlelekef If nmyltrdrrhevarllnlseRQvKIwfQNrrMKMkK mnkeq,

[0148] harstRKKRcpytkyqtlelekef If nmyltrdrryevarilnlteRQvKIwfQNrrmkm, taksgRKKRcpytkhqtlelekef If nmyltrerrleisktinltdRQvKIwfQNrrMKlkK mnren, ekeskEeiksd, taksgRKKRcpytkhqtlelekef If nmyltrerrleisrsvhltdRQvKIwfQNrrMKlkK mnren, IgsgqRqsASeREklRMrtlar, paggqRqsASeREKIRMrtlar, msvqrRrkaSeREklRMrtlad,

[0149] ikktrRlkANnRERnRMhnlnaaldalrevlpt fpedakltKietlr, itkagRrmfpamrvkisgldphqqyyiamdivpvdnkryryvyhsskwmvagnadspvpprvyi,

[0150] pdspasgetwmrqvisf dklkltnnelddqghiilhsmhkyqprvhvirkdcgddlspikpv psgegvkaf sfpetvfttVTAyqnqqitrlkidrnpFakGFrdsgr, itkagRrmfpamrvkitgldphqqyyiamdivpvdnkryryvyhsskwmvagnadspvpprv yihpdslasgdtwmrqvvSf dKLkltnnelddqghiilhsmhkyqprvhvirkdf ssdlspt kpvpvgdgvkt f nfpetvfttvTAyqnqqitrlkidrnpFakGFrdsgr, itkagRrmfpamrvkisgldphqqyyiamdivpvdnkryryvyhsskwmvagnadspvpprv yihpdspasgetwmrqvisf dklkltnnelddqghiilhsmhkyqprvhvirkdcgddlspi kpvpsgegvkaf sfpetvfttvTAyqnqqitrlkidrnpFakGFrdsgr, itkagRrmfpamrvkitgldphqqyyiamdivpvdnkryryvyhsskwmvagnadspvpprv yihpdslasgdtwmrqvvSf dKLkltnnelddqghiilhsmhkyqprvhvirkdf ssdlspt kpvpvgdgvkt fnf pet vfttvTAyqnqqitrlkidrnpFakGFrdsgr, itksgRrmfptirvsf sgvdpeakyivlmdivpvdnkryryayhrsswlvagkadpplparl yvhpdspftgeqllkqmvsf ekvkltnneldqhghiilnsmhkyqprvhiikkkdhtaslln Ikseef rt f ifpetvftavTAyqnqlitklKidsnpFakGFrdssr,

[0151] vtkagRrmfpt f qvklf gmdpmadymllmdfvpvddkryryafhssswlvagkadpatpgrv hyhpdspakgaqwmkqivsf dklkltnnllddnghiilnsmhryqprfhvvyvdprkdseky aeenf kt fvf eetrftavTAyqnhritqlkiasnpFakGF,

[0152] vtkagRrmfpt f qvklf gmdpmadymllmdfvpvddkryryafhssswlvagkadpatpgrv hyhpdspakgaqwmkqivsf dklkltnnllddnghiilnsmhryqprfhvvyvdprenf kt f vf eetrftavTAyqnhritqlkiasnpFakGF, or vtkagRrmfpt f qvklf gmdpmadymllmdfvpvddkryryafhssswlvagkadpatpgrv hyhpdspakgaqwmkqivsf dklkltnnllddnghiilnsmhryqprfhvvyvdprkdseky aeenf kt fvf eetrftavTAyqnhritqlkiasnpFakGFrdcdp.

[0153] A DNA binding peptide may be derived at least in part of at least a part of the following protein domains: Fox DNA binding motif, FOXC1, C2H2 type zinc finger, Zinc finger, C2H2 type, Zinc finger double domain, C2H2 type zinc finger, Homeobox domain, Myb like DNA binding domain, Helix loop helix DNA binding domain, Zinc finger, C4 type (two domains), Myb like DNA binding domain, bZIP transcription factor, Basic region leucine zipper, Ligand binding domain of nuclear hormone receptor, Zinc finger of C2H2 type, Homeobox KN domain, HMG (high mobility group) box, Domain of unknown function (DUF1898), Fork head domain, Ets domain, AP2 domain, GATA zinc finger, Pou domain N terminal to homeobox domain, KRAB box, Fungal Zn (2) Cys (6) binuclear cluster domain, Ankyrin repeat, PAS fold, Rel homology domain (RHD), GTF2I like repeat, LIM domain, C2H2 type zinc finger domain, ' Paired box' domain, MH1 domain, SRF type transcription factor (DNA binding and dimerization domain), AT hook motif, T box, IPT / TIG domain, Ankyrin repeats (3 copies), Interferon regulatory factor transcription factor, BTB / POZ domain, Sterile alpha motif (SAM) / Pointed domain, No apical meristem (NAM) protein, PAS fold, CUT domain, WRKY DNA binding domain, bZIP Maf transcription factor, Fungal specific transcription factor domain, B3 DNA binding domain, Sigma 70, region 4, E2F / DP family winged helix DNA binding domain, Interferon regulatory factor 3, N terminal CTNNB1 binding, Sigma 70 region 2, CTF / NF I family transcription modulation region, HSF type DNA binding, P53 DNA binding domain, C2H2 type zinc finger (2 copies), Ankyrin repeat, Helix turn helix, OAR domain, Runt domain, pKID domain, P53 tetramerisation motif, Nuclear factor I protein pre N terminus, Sigma 70 region 3, Response regulator receiver domain, Sigma 70 factor, region 1.2, Transcription factor TFIID (or TATA binding protein, TBP), SH2 domain, MarR family, STAT protein, all alpha domain, STAT protein, DNA binding domain, Ankyrin repeats (many copies), DM DNA binding domain, RFX DNA binding domain, SCAN domain, MH2 domain, Winged helix DNA binding domain, Tesmin / TSOl like CXC domain, Transcriptional regulatory protein, C terminal, Myb / SANT like DNA binding domain, Dof domain, zinc finger, MerR family regulatory protein, MerR HTH family regulatory protein, MarR family, SAND domain, Transcription factor TFIIB repeat, TCP family transcription factor, Domain of unknown function (DUF3371), PHD finger, Sigma 70, non essential region, Hairy Orange, STAT protein, protein interaction domain, Myogenic Basic domain, Auxin response factor, Bacterial regulatory proteins, gntR family, Bacterial regulatory proteins, luxR family, ARID / BRIGHT DNA binding domain, Transcription factor AP 2, Bacterial regulatory proteins, lacl family, Helix turn helix domain, Hepatocyte nuclear factor 1 (HNF 1), N terminus, Holliday junction regulator protein family C terminal repeat, K box region, Myc amino terminal region, PAS domain, Estrogen receptor beta, Zinc finger double stranded RNA binding, Bacterial regulatory helix turn helix proteins, AraC family, Periplasmic binding proteins and sugar binding domain of Lacl family, Periplasmic binding protein like domain, Sigma 70, region 4, Glucocorticoid receptor, Alcohol dehydrogenase transcription factor Myb / SANT like, TEA / ATTS domain family, Runx inhibition domain, Homeodomain leucine zipper encoding, Homez, Myc leucine zipper domain, AUX / IAA family, Winged helix turn helix DNA binding, LAG1, DNA binding, Myb / SANT like DNA binding domain, BED zinc finger, Beta trefoil DNA binding domain, TFIIB zinc binding, GATA type transcription activator, N terminal, Periplasmic binding protein domain, CP2 transcription factor, Paired box protein 2 C terminal, Jun like transcription factor, SBP domain, G box binding protein MFMR, Hox protein A13 N terminal, Histone like transcription factor (CBF / NF Y) and archaeal histone, Forkhead N terminal region, C myb, C terminal, SOX transcription factor, Homeobox associated leucine zipper, GCM motif protein, Wilm's tumor protein, Myogenic determination factor 5, lysR family, Core histone H2A / H2B / H3 / H4, Hox9 activation region, MYB CC type transfactor, LHEQLE motif, MerR, DNA binding, Homeodomain like domain, Seed dormancy control, LMSTEN motif, HTH domain, HNF3 C terminal domain, Androgen receptor, Nuclear receptor repeat, helix turn helix, Psq domain, PBC domain, Zinc finger associated domain (zf AD), Engrailed homeobox C terminal signature domain, Hepatocyte nuclear factor 1 (HNF 1), beta isoform C terminus, Transcription factor protein N terminal, Iron dependent repressor, N terminal DNA binding domain, RFX1 transcription activation region, Maf N terminal region, SAM domain (Sterile alpha motif), CXXC zinc finger domain, Sox developmental protein N terminal, Domain of unknown function (DUF3446), P53 transactivation motif, Oestrogen receptor, Homeobox protein distal less like N terminal, DeoR like helix turn helix domain, Vertebrate heat shock transcription factor, Sp100 domain, Crp like helix turn helix domain, Sox C terminal transactivation domain, LysR substrate binding domain, Transcriptional regulator, Fungal specific transcription factor domain, IQ calmodulin binding motif, Protein of unknown function DUF260, Zinc finger, C3HC4 type (RING finger), PEA3 subfamily ETS domain transcription factor N terminal domain, Nuclear / hormone receptor activator site AF 1, Zinc finger, C3HC4 type (RING finger), PPAR gamma N terminal region, CCAAT binding transcription factor (CBF B / NF YA) subunit B, Cyclic nucleotide binding domain, T box transcription factor, Bacterial regulatory proteins, crp family, Ring finger domain, START domain, Ferric uptake regulator family, Cro / Cl type HTH DNA binding domain, Iron dependent repressor, metal binding and dimerisation domain, bHLH MYC and R2R3 MYB transcription factors N terminal, Bacterial regulatory protein, Fis family, SET domain, Death domain, Hypoxia inducible factor 1, KilA N domain, ' Cold shock ' DNA binding domain, Otxl transcription factor, Caudal like protein activation region, FHA domain, Poly (ADP ribose) polymerase and DNA Ligase Zn finger region, HIF 1 alpha C terminal transactivation domain, Protein of unknown function (DUF3528), Helicase conserved C terminal domain, THAP domain, Sugar specific transcriptional regulator TrmB, Arc like DNA binding domain, Arginine repressor, DNA binding domain, Neuronal helix loop helix transcription factor, Epstein Barr virus nuclear antigen 1, DNA binding domain, FeoC like transcriptional regulator, Methyl CpG binding domain, DMRTA motif, Cyclin, N terminal domain, Bacterial regulatory proteins, tetR family, HxlR like helix turn helix, ZF HD protein dimerisation region, BESS motif, Domain of unknown function (DUF4074), Transcriptional regulator PadR like family, linker histone Hl and H5 family, GyrI like small molecule binding domain, Arginine repressor, C terminal domain, MYND finger, Ribbon helix helix protein, copG family, SNF2 family N terminal domain, CCT motif, Basic leucine zipper C terminal, RNA recognition motif, (a. k. a. RRM, RBD, or RNP domain), RNA recognition motif, (a. k. a. RRM, RBD, or RNP domain), Oestrogen type nuclear receptor final C terminal, Ethylene insensitive 3, RNA recognition motif (a. k. a. RRM, RBD, or RNP domain), Plant zinc cluster domain, Core binding factor beta subunit, Plant protein of unknown function (DUF822), ELK domain, Progesterone receptor, Paired box protein 7, KNOX2 domain, Domain of unknown function (DUF296), Autoinducer binding domain, CG 1 domain, FCD domain, ATPase family associated with various cellular activities (AAA), CoA binding domain, BAH domain, TFIIE alpha subunit, Putative DNA binding protein N terminus, KNOX1 domain, Tc5 transposase DNA binding domain, WRC, TrkA C domain, Hepatocyte nuclear factor 1 (HNF 1), alpha isoform C terminus, HIRAN domain, Zinc knuckle, GA binding protein alpha chain, CarD like / TRCF domain, arsR family, NDT80 / PhoG like DNA binding family, Homeobox prospero like protein (PROX1), Poxvirus D5 protein like, WGR domain, Paired amphipathic helix repeat, F box like, Antitermination protein, PADR1 (NUC008) domain, Ataxin 1 and HBP1 module (AXH), Protein of unknown function, DUF573, hAT family dimerisation domain, pre mRNA splicing factor component, Domain of unknown function (DUF4371), Transcription initiation factor IIF, alpha subunit (TFIIF alpha), NLS binding and DNA binding and dimerisation domains of Nrfl, CodY GAF like domain, Transcriptional activator of glycolytic enzymes, JmjC domain, hydroxylase, BRCA1 C Terminus (BRCT) domain, CASP C terminal, Sigma 54 interaction domain, Poly (ADP ribose) polymerase catalytic domain, DDE superfamily endonuclease, IclR helix turn helix domain, TAZ zinc finger, tify domain, zinc finger of a C2HC type, ECF sigma factor, PRD domain, Domain of unknown function (DUF3432), Penicillinase repressor, Poly (ADP ribose) polymerase, regulatory domain, Trp repressor protein, Herpesvirus ICP4 like protein N terminal region, QLQ, B12 binding domain, FadR C terminal domain, DeoR C terminal sensor domain, Gal4 like dimerisation domain, Brfl like TBP binding domain, E2 (early) protein, C terminal, STE like transcription factor, Tetracycline repressor, C terminal all alpha domain, Nrfl activator activation site binding domain, CodY helix turn helix domain, Bacterial dnaA protein helix turn helix, Copper fist DNA binding domain, Zinc finger, C3HC4 type (RING finger), GAGA binding protein like family, Telomere repeat binding factor (TRF), AAA domain (dynein related subfamily), Transcription factor PAP1, Vertebrate interleukin 3 regulated transcription factor, Aminotransferase class I and II, F box domain, YABBY protein, PAS fold, RNA polymerase Rpbl, domain 5, Divergent CCT motif, Sigma 70 factor, region 1.1, HD ZIP protein N terminus, RNA polymerase Rpbl, domain 4, Bacteriophage CII protein, SKI / SNO / DAC family, CENP B N terminal DNA binding domain, Double sex mab3 related transcription factor 1, UTRA domain, Floricaula / Leafy protein, Zinc knuckle, jmjN domain, RNA polymerase Rpbl, domain 2, RNA polymerase Rpbl, domain 3, Zfx / Zfy transcription activation region, MEKHLA domain, Transcription initiation factor IIF, beta subunit, Type III restriction enzyme, res subunit, Zinc finger, C2HC type, RNA polymerase Rpbl, domain 1, Bromodomain, BAF1 / ABF1 chromatin reorganising factor, NikR C terminal nickel binding domain, POU domain, class 2, associating factor 1, DDT domain, Histone acetylation protein, Transcription factor IIA, alpha / beta subunit, Fungal protein of unknown function (DUF1752), B box zinc finger, Bacterial transcriptional regulator, MULE transposase domain, Creb binding, Bacterial dna Aprotein, c SKI Smad4 binding domain, ROK family, Metal binding domain of Ada, Transcription initiator DNA binding domain IBD, IstB like ATP binding protein, DEAD / DEAH box helicase, Peptidase S24 like, Sporulation initiation factor SpoOA C terminal, Met Apo repressor, MetJ, RWP RK domain, TRCF domain, Chaperone of endosialidase, Zinc finger, ZZ type, FeoA domain, RNA polymerase Rpbl C terminal repeat, BEN domain, Transcription factor AFT, AsnC family, PAS domain, PurA ssDNA and RNA binding protein, MT A70, Zinc finger protein, KIX domain, Minimal binding motif of Hap4 for binding to Hap2 / 3 / 5, Histidine kinase, DNA gyrase B, and HSP90 like ATPase, AsnC type helix turn helix domain, Domain of unknown function (DUF702), Domain of Unknown Function (DUF902), STAT1 TAZ2 binding domain, Inhibitor of growth proteins N terminal histone binding, C terminal domain of methyl CpG binding protein 2 and 3, RNA polymerase beta subunit, Homeobox protein, Putative binding domain, Cupin like domain, TOBE domain, SWIM zinc finger, Putative helix turn helix protein, YlxM / pl3 like, Cytosine specific DNA methyltransferase replication foci domain, Doublesex dimerisation domain, GAGA factor, RNA polymerase Rpb2, domain 3, Domain of unknown function (DUF313), Churchill protein, FAR1 DNA binding domain, RING H2 zinc finger, Rapl, DNA binding, Putative ATPase subunit of terminase (gpP like), AraC like ligand binding domain, GRF zinc finger, RNA polymerase Rpb2, domain 4, Transferrin, Integrase core domain, SPRY domain, AN1 like Zinc finger, SWIRM domain, RNA polymerase Rpb2, domain 6, RNA polymerase Rpb2, domain 5, WD domain, G beta repeat, Helix turn helix domain of resolvase, Centromere protein B dimerisation domain, Signal transducer and activator of transcription 2 C terminal, GRAS family transcription factor, Oxygenase domain of the 2OGFeDO superfamily, QacR like protein, C terminal region, Histone deacetylase domain, Transcription factor DP, LisH, LexA DNA binding domain, RecF / RecN / SMC N terminal domain, Domain of unknown function DUF120, DnaA N terminal domain, RING type zinc finger, LisH dimerisation motif, Brinker DNA binding domain, Amino acid kinase family, RNA polymerase Rpbl, domain 7, Protein kinase domain, N terminal domain of DPF2 / REQ, Transcription factor Vhrl, Glycosyl hydrolase family 14, Domain of unknown function (DUF2028), mTERF, RNA polymerase Rpb2, domain 7, RNA polymerase Rpbl, domain 6, Protein tyrosine kinase, Associated with HOX, AAA domain (Cdc48 subfamily), Fushi tarazu (FTZ), N terminal region, RING variant domain, PB1 domain, CBS domain, RNA polymerase Rpb2, domain 2, Lectin C type domain, Ubiquitin C terminal hydrolase 37 receptor binding site, CAT RNA binding domain, Phosphoribosyl transferase domain, Phi 29 like late genes activator (early protein GP4), Protein of unknown functionDUF13, C 5 cytosine specific DNA methylase, Arginase family, Alpha / beta hydrolase family, Nucleopolyhedrovirus late expression factor 3 (LEF 3), H NS histone family, TFIIE beta subunit core domain, PBP superfamily domain, PLATZ transcription factor, Complexl_LYR like, Histidine kinase, DNA gyrase B, and HSP90 like ATPase, BSD domain, Sec7 domain, Sigma 54 modulation protein / S30EA ribosomal protein, TipAS antibiotic recognition domain, Thiolase, C terminal domain, PCI domain, Zn finger in Ran binding protein and others, DMAP1 binding Domain, Mannitol dehydrogenase Rossmann domain, GAF domain, DNA binding protein S1FA, Protein of unknown function (DUF3591), CW type Zinc Finger, ARC105 or Medl5 subunit of Mediator complex non fungal, Oxidoreductase family, NAD binding Rossmann fold, Semialdehyde dehydrogenase, NAD binding domain, Guanine nucleotide exchange factor in Golgi transport N terminal, Cytochrome C and Quinol oxidase polypeptide I, E2 (early) protein, N terminal, NOPS (NUC059) domain, phosphotransferase system, EIIB, YL1 nuclear protein, KorB domain, 6 0 methylguanine DNA methyltransferase, DNA binding domain, Mannitol dehydrogenase C terminal domain, Poxvirus early transcription factor (VETF), large subunit, GAF domain, Herpesvirus transcription activation factor (transactivator), Leucine Rich repeat, Transcription factor Opil, ATP cone domain, P protein C terminus, DHHC palmitoyltransferase, YsiA like protein, C terminal region, XPA protein N terminal, CoA binding domain, dimerisation domain, Acetyltransferase (GNAT) family, TLC domain, Phosphotransferase system, EIIC, YL1 nuclear protein C terminal domain, Ribosomal protein L16p / L10e, Domain of unknown function (DUF4195), G patch domain, Plus 3 domain, Bacterial purine repressor, N terminal, Rapl C terminal domain, Zinc binding, KH domain, HAMP domain, GAF domain, Tryptophan RNA binding attenuator protein, F / Y rich N terminus, Transcriptional activator TraM, XPA protein C terminus, Exonuclease, Protein of unknown function (DUF619), Pyridine nucleotide disulfide oxidoreductase, His (2) Cys (2) zinc finger, Zinc carboxypeptidase, Bacterial transferase hexapeptide (six repeats), DExH box splicing factor binding site, 6 0 methylguanine DNA methyltransferase, ribonuclease like domain, Bacterial DNA binding protein, OTU like cysteine protease, Mating type protein MAT alpha 1, B block binding subunit of TFIIIC, MamL 1 domain, KH domain, Firmicute transcriptional repressor of class III stress genes (CtsR), Histidine kinase, Zinc finger of the MIZ type in Nse subunit, Metallo beta lactamase superfamily, Basic membrane protein, F / Y rich C terminus, Eukaryotic translation initiation factor eIF2A, UBA / TS N domain, BTB And C terminal Kelch, SAM domain (Sterile alpha motif), Aftl osmotic stress response (OSM) domain, Pyridine nucleotide disulfide oxidoreductase, Interferon induced 35 kDa protein (IFP 35) N terminus, Protein of unknown function (DUF2817), Sin3 binding region of histone deacetylase complex subunit SAP30, HrcA protein C terminal domain, Magnesium chelatase, subunit Chll, Archaeal ATPase, Transcriptional regulator DELLA protein N terminal, Maltose acetyltransferase, Suppressor of cytokine signalling, SI RNA binding domain, 3H domain, ABA / WDS induced protein, Transcription factor CRF1, Domain of unknown function (DUF3518), Recombinase Flp protein N terminus, Beta lactamase superfamily domain, PHD like zinc binding domain, Myelin gene regulatory factor C terminal domain 1, Aldehyde dehydrogenase family, Nuclear pore complex assembly, Putative GTPase activating protein for Arf, Anti repressor SinI, Antidote toxin recognition MazE, SSXRD motif, CBF / Mak21 family, L lysine 6 monooxygenase (NADPH requiring), Adenylate and Guanylate cyclase catalytic domain, Flagellar transcriptional activator (FlhD), PTS system fructose IIA component, AAA domain, Stage III sporulation protein D, Transcription factor / nuclear export subunit protein 2, NusA N terminal domain, Reverse transcriptase like, SMC proteins Flexible Hinge Domain, short chain dehydrogenase, Glycerol 3 phosphate responsive antiterminator, alpha / beta hydrolase fold, Recombinase Flp protein, Domain of unknown function (DUF3425), His Kinase A (phospho acceptor) domain, Family description, PHD zinc finger like domain, PTS HPr component phosphorylation site, DDE superfamily endonuclease, Transcriptional enhancer, Asx hm domain, DnaJ domain, SPFH domain / Band 7 family, Myelin gene regulatory factor C terminal domain 2, Proline dehydrogenase, Cro, Domain of unknown function (DUF4171), CHY zinc finger, Pyridine nucleotide disulfide oxidoreductase, Protein phosphatase 2C, YcdC like protein, C terminal region, Ribosomal protein L35Ae, C5HC2 zinc finger, Transcription and export related complex subunit, Uncharacterized protein family (UPF0121), NusA like KH domain, PAS domain, AAA domain, Domain of unknown function (DUF3594), Alpha / beta hydrolase family, Peptidase family Ml, GDSL like Lipase / Acylhydrolase, Complex 1 protein (LYR family), Winged helix turn helix, Ubiquitin associated domain (UBA), Winged helix turn helix transcription repressor, HrcA DNA binding, Transcriptional regulator, Serpentine type 7TM GPCR chemoreceptor Srh, Putative Sin3 binding protein, Thiolase, N terminal domain, CpG binding protein zinc finger C terminal domain, PucR C terminal helix turn helix domain, PLU 1 like protein, EVE domain, SPT2 chromatin protein.

[0154] The hybrid peptide must be comprised from at least a stretch of amino acids that comprise a DNA binding stretch and at least a stretch of amino acids that comprise an NLS amino acid stretch, in some embodiments. In some embodiments, the hybrid peptide, is included in the formulation, embedded in the lipid nanoparticle, partially embedded in the lipid nanoparticle, prehybridized with the DNA, ionically, electrostatically, or covalently coupled to one or more moieties in the formulation and / or is comprised of a plethora of DNA binding stretches and a plethora of NLS sequences with or without interweaving, flanking, or intervening and flanking spacer sequences. In some specific embodiments, two NLS sequences are the outmost flanking sequences and the DNA binding sequences are contained in the core of the peptide, the NLS sequences are separated from the DNA binding sequences by spacers of at least 6 amino acids which are flexible or semi flexible spacers.

[0155] In addition to the hybrid peptide, the gene therapy system generally includes at least one DNA cassette or a plethora of DNA cassettes and said DNA cassette or cassettes may include at least one protein binding site which can interact with at least a part of the hybrid peptide, and preferably multiple protein binding sites that can interact with one or more amino acid stretches on the hybrid peptide or on different hybrid peptide, in some embodiments. Said hybrid peptide interacting sequence or protein binding site can be comprised at least in part from, at least a part of the following sequences.

[0156] Table 5

[0157]

[0158]

[0159]

[0160]

[0161]

[0162]

[0163]

[0164] The protein-binding sequence of DNA can be in general any protein binding sequence of mammalian and most ideally human DNA, which is known to bind proteins parts of proteins or peptides that are naturally present in human cells or that can be introduced into humans cells by a process of infection or oncogenesis. Said protein-binding sequences of DNA may be introduced as a single stretch, or as multiple stretches separated by other DNA elements, such as for example the therapeutic transgene. In some specific embodiments of the present invention, the proteinbinding sequences of DNA may flank the gene of interest and critical regulatory elements and may be introduced on either side of the gene of interest from one on either side to up to 10 on either side with or without separation by other DNA sequences to facilitate binding of one or more DNA binding peptides or proteins.

[0165] Preferably, in some embodiments, the DNA cassette should include protein binding sequences that are known to bind proteins expressed in the cell type targeted by the gene therapy or at least predominantly targeted by the gene therapy to enable the opportunity for native transport to augment hybrid peptide mediated transport. As an example, an adipocyte-targeting gene therapy or a gene therapy vector administered subcutaneously in an area predominantly occupied by adipocytes can use a protein binding sequence in the DNA cassette, which is comprised at least in part from, at least a part of DNA sequences that are known to bind proteins that are expressed or expressed at least a moderate level, and most ideally a high level, in adipocytes to facilitate optimal transport. Similarly, NLS sequences for the hybrid peptides can be optionally derived from NLS sequences that are naturally utilized by adipocytes in proteins that are expressed or expressed at a high level in adipocytes. Multiple different hybrid peptides can be used in a formulation. Each of the hybrid peptides used, if multiple are used, or the hybrid peptide, if only one type is used, can be in a ratio of 0.1 to 1000 to the DNA protein-binding stretch, but is preferably in a ratio of 0.2 to 12 to the DNA protein-binding stretch such that the peptide is present in a slight excess or the DNA binding sites are present in a slight excess, in some embodiments. Most preferably, the peptide is present in a slight excess of approximately 1.0 to approximately 6 to each of its corresponding DNA binding stretch partners, in some embodiments. Said parameter can be defined as the critical binding number or the critical pairing number (terms are used interchangeably for the purposes of this invention) where a pair is defined as a DNA binding peptide stretch and DNA protein binding sequence such that if the hybrid peptide contains a single DNA binding peptide stretch and the therapeutic DNA cassette contains a single DNA protein-binding sequence, the pairing number is 1, meaning the hybrid peptide is present in a ratio of 1: 1 to the DNA protein binding sequence. Similarly, for example, if the hybrid peptide contains 4 DNA binding amino acid stretches and they are identical and bind to 2 identical protein-binding DNA stretches on the therapeutic cassette, the pairing number is 2 meaning the hybrid peptide is present in a ratio of 2: 1 to the DNA proteinbinding sequence. It is understood for the purposes of this invention that since the therapeutic DNA cassette can have several different DNA protein binding sequences and since the hybrid peptide may also be comprised of several DNA binding amino acid sequences the pairing number or binding number is calculated based on each pair individually, as such a single formulation may have several pairing numbers. In some embodiments of the present invention the pairing numbers can range of 0.1 to 150, but preferably the peptide sequences are present in excess to each of their target DNA protein-binding sites, as such most ideally the binding numbers are all in excess of 1 and all approximately below 6, in some embodiments.

[0166] The protein binding sites can be inserted into the genetic cassette or the genetic cassette sequence can be optimized to include the protein binding sites without adding nucleotides. As an example, a TCA codon can be changed to a TCG codon to enable CpG island binding by a peptide that mimics TLR9. For such an example, the hybrid peptide can contain a leucine rich repeat such as xLxxLxLxxNxLxxLPxxxFx, where x (or X) is any amino acid. Alternatively, naturally occurring CpGs or CpG islands can be left in the genetic cassette without optimizing said islands for hypoimmunogenicity. Co-administration of said cassettes with the partner hybrid peptide can reduce the resulting TLR9 activation since the TLR9 binding sites are occupied by the hybrid peptide. At the same time, transport to the nucleus can be enhanced through the hybrid peptide' s NLS signal, which may be located downstream of the DNA binding site following a spacer of 0-24 amino acids.

[0167] For the purposes of this invention an amino acid labelled X in a stretch of amino acids is any natural amino acid occurring in the human body.

[0168] For the purposes of this invention a DNA base or a base in a DNA sequence labelled N in a stretch of DNA is any DNA base A, T, C, or G. And generally, in a sequence of DNA the following degenerate base code is utilized:

[0169] Y = C, T

[0170] R = A, G

[0171] M = A, C

[0172] K = G, T

[0173] S = C, G

[0174] W = A, T

[0175] H = A, C, T

[0176] B = C, G, T

[0177] V = A, C, G

[0178] D = A, G, T

[0179] N = A, C, G, T

[0180] In some specific embodiments of the present invention the therapeutic formulation can contain a full hybrid peptide, which may be comprised of at least 4 consecutive amino acids of the NLS sequence KQRDAEHRDRTKKKKRSRSRDRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNKVKSRY RSRSRSQSPPKDRKDRDK and at least 4 consecutive amino acids of the DNA binding stretch CSTLNFTLDLSRNNLVTVQPEMFAQLSHLQCLRLSHNCISQAVNGSQFLPLTGLQVLDLSHN KLDLYHEHSFTELPRLEALDLSYNSQPFGMQGVGHNFSFVAHLRTLRHLSLAHNNIHSQVSQ QLCSTSLRALDFSGNALGHMWAEGDLYLH or at least 4 consecutive amino acids of the NLS sequence MMPNKVRKIGELVRYLNTNPVGGLLEYARSHGFAAEFKLVDQSGPPHEPKFVYQAKVGGRWF PAVCAHSKKQGKQEAADAALRVLIGENEKAER, at least 4 consecutive amino acids of the DNA binding stretch SGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCI INKVTRNRCQYCRLQKCFEVGMSKEA VRNDRNKKKKEVKEEGSPDSYE, and at least 4 consecutive amino acids of the NLS sequence GRNRAPELGAPGIQKKKR or at least 4 consecutive amino acids of the NLS sequence PRRTTRRHPNTQQRASKKKPK, at least 4 consecutive amino acids of the spacer sequence AKKSKTAAKKNDKEAAG, and at least 4 consecutive amino acids of the DNA binding stretch RLAANARERRRMHGLNHAFDQLRNVIPSFNNDKKLSK.

[0181] In another specific embodiment the full hybrid peptide can be comprised of at least 4 consecutive amino acids of the NLS sequence KRPAATKKAGQAKKK, at least 4 consecutive amino acids of the spacer sequence DEKTEESDTDRLLSSDHEKSHSNLGV, at least 4 consecutive amino acids of the DNA binding stretch RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASR, at least 4 consecutive amino acids of the spacer sequence GGGGSGGGGSGGGGSGGGGS, and at least 4 consecutive amino acids of the NLS sequence KRMNAFMVWAQAARRK. Alternatively, the full hybrid peptide can be comprised of up to 3 NLSs optionally interspersed with spacers and up to 3 DNA binding stretches optionally interspersed with spacers, such that the NLSs are comprised of at least 4 consecutive amino acids from each of the following sequences RQARRNRRRRWR, CYGSKNTGAKKRKIDDA, RKHKTNRKPR, spacers which may be comprised of at least 4 consecutive amino acids from each of the following sequences GSAGSAAGSGEF, SDQEAKPSTEDLG, RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNT, and DNA binding sites that are comprised of at least 4 consecutive amino acids from each of the following sequences RKLKNRVAAQTARDRK, KRKRRGNLPKESVKILRDWLYLHRYNAYPSEQEKLSLSGQTNLSVLQICNWFINARRR, AWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTLDPQSEDMFDNGSFLRRRKR.

[0182] Alternatively, the full hybrid peptide can be comprised of up to 3 NLSs optionally interspersed with spacers and up to 3 DNA binding stretches optionally interspersed with spacers, such that the NLSs are comprised of at least 4 consecutive amino acids from each of the following sequences SQKHLQINQTFEELRLVT, RKP VT AQE RQRE RE E KRRRRQE RAKE RE KRRQE RE R, KRPMNAF I VWS RD QRRK, spacers which may be comprised of at least 4 consecutive amino acids from each of the following sequences APELLGGP, PVPSTPPTPSPSTPPTPSPSC, AKAEAGAEAGGGAGPGAEDEAGRGAVGDPELGDPPAAPQ, and DNA binding sites that are comprised of at least 4 consecutive amino acids from each of the following sequences PLWRRDGTGHYLCNACGLYHKMNGQNRPLIKPTSCANCQTTTTTLWRRNANGDPVCNACGLY YKLHNINRPLTMKKEGIQTRNRKM, LTTEADSGY, KTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVME YHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPV WIVHGSQ. Alternatively, the full hybrid peptide can be comprised of an NLS sequence and a DNA binding stretch from a protein moderately to highly expressed in adipocytes and include the sequence EYQSAIKVEPASPPYYSEKTQLYNRPHEEPSNSLMAISGFHYGVHACEGCKGFFRRTIRLKL I YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEK with or without intervening spacer sequences separating the NLS and DNA binding stretch. Alternatively, the full hybrid peptide can be comprised of an NLS, a DNA binding stretch from a protein moderately to highly expressed in adipocytes, and an NLS and include the sequence PAAKRVKLDRENHSEIERRRRNKMTAYITELSDMVPTCPDKPAAKRVKLD with or without intervening spacer sequences separating the NLS and DNA binding stretch. Alternatively, the full hybrid peptide can be comprised of an NLS, a spacer sequence, and a DNA binding stretch from a protein moderately to highly expressed in adipocytes and include the sequence RRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAEG GGGSGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGE ILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVF QVKTLSLPVVVIVHGSQ with or without intervening spacer sequences separating the NLS and DNA binding stretch. Alternatively, the full hybrid peptide can be comprised of an NLS, a spacer, a DNA binding stretch from a protein moderately to highly expressed in adipocytes, a spacer, and an NLS and include the sequence SQKHLQINQTFEELRLVTGGGGSRERNNIAVRKSRGGGGSSQKHLQINQTFEELRLVT

[0183] with or without intervening spacer sequences separating the NLS and DNA binding stretch. In some embodiments of the present invention the formulation can contain one or more hybrid peptides, at least one of which is the full hybrid peptide which can be comprised of 3 NLSs interspersed with spacers, a DNA binding stretch from a protein moderately to highly expressed in adipocytes, and 3 NLSs interspersed with spacers, which contains RRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAEG SAGSAAGSGEFPAAKRVKLDGSAGSAAGSGEFSQKHLQINQRFEELRLITKRRHRTTFTSLQ LEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRKSQKHLQINQRFEELRL ITGSAGSAAGSGEFPAAKRVKLDGSAGSAAGSGEFRRTIRLKLI YDRCDLNCRIHKKSRNKC QYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAE. Alternatively, the full hybrid peptide can be comprised of 3 NLSs, 3 DNA binding stretches from one or more proteins moderately to highly expressed in adipocytes, and 3 NLSs, all interspersed with spacers, which contains SQKHLQINQTFEELRLVTGGGGSGGGGSGGGGSEYQSAIKVEPASPP YYSEKTQLYNRPHEE PSNSLMAIGGGGSGGGGSGGGGSPAAKRVKLDGGGGSGGGGSGGGGSSGFHYGVHACEGCKG FFRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKGGG GSGGGGSGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNEC SGEILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNE LVFQVKTLSLPVWIVHGSQGGGGSGGGGSGGGGSRERNNIAVRKSRGGGGSGGGGSGGGGS PAAKRVKLDGGGGSGGGGSGGGGSEYQSAIKVEPASPP YYSEKTQLYNRPHEEPSNSLMAIG GGGSGGGGSGGGGSSQKHLQINQTFEELRLVT. Alternatively, the full hybrid peptide can be comprised of up to 3 repeats of an NLS-DNA binding stretch unit derived from proteins moderately to highly expressed in adipocytes and connected by flexible spacers, with an amino acid sequence that contains CYGSKNTGAKKRKIDDAKSNPSKRHRDGGGGSGGGGSGGGGSGGGGSCYGSKNTGAKKRKID DAKSNPSKRHRDGGGGSGGGGSGGGGSGGGGSCYGSKNTGAKKRKIDDAKSNPSKRHRD. Alternatively, the full hybrid peptide can be comprised of up to 3 different NLS-DNA binding stretch units derived from proteins moderately to highly expressed in adipocytes and connected by flexible spacers, with an amino acid sequence that contains

[0184] KRMNAFMVWAQAARRKSGFHYGVHACEGCKGFFRRTIRLKLI YDRCDLNCRIHKKSRNKCQY CRFQKCLAVGMSHNAIRFGRMPQAEKEKGGGGSGGGGSGGGGSKRPAATKKAGQAKKKNHNI LERQRRNDLRSSFLTLRDHVPELVKNEKAAKGGGGSGGGGSGGGGSCYGSKNTGAKKRKIDD AKSNPSKRHRD. Alternatively, the full hybrid peptide can be comprised of one or multiple DNA binding stretches and one or multiple NLS sequences interspersed with spacers, which is PAAKRVKLDGGGGSPAAKRVKLDGGGGSPAAKRVKLDGGGGSKSNPSKRHRDGGGGSGGGGS KSNPSKRHRDGGGGSGGGGSKSNPSKRHRDGGGGSPAAKRVKLDGGGGSPAAKRVKLDGGGG SPAAKRVKLD. Alternatively, the full hybrid peptide can be comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is KRMNAFMVWAQAARRKAPELLGGPCKRKTTNADRRKAAPELLGGPGRNRAPELGAPGIQKKK RAPELLGGPRLMKNREAARECRGGGGSRRSKNRIAAQRCRKRKGGGGSRREKNKVAAARCRN KKAPELLGGPGRNRAPELGAPGIQKKKRAPELLGGPCKRKTTNADRRKAAPELLGGPKRMNA FMVWAQAARRK. Alternatively, the full hybrid peptide can be comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is SQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRL VTGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEIL NNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQV KTLSLPVWIVHGSQGSAGSAAGSGEFKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQ QAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEK FTVLFESQFSVGSNELVFQVKTLSLPVWIVHGSQGSAGSAAGSGEFKTQTKFAATVRLLVG GKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNM SLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPVWIVHGSQGGGGSSQ KHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVT

[0185] . Alternatively, the full hybrid peptide can be comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is GKKKKGKPGKRREQRKKKRRTGGGGSGGGGSGGGGSGGGGSSGFHYGVHACEGCKGFFRRTI RLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKGGGGSGGGG SGGGGSGGGGSRREKNKVAAARCRNKKGGGGSGGGGSGGGGSGGGGSKRRHRTTFTSLQLEE LEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRK. Yet alternatively, the full hybrid peptide can be comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is CYGSKNTGAKKRKIDDAGGGGSGGGGSGGGGSRRERNKIAAAKCRNKKRWPESPKAQASSVP TAQPQAEGSLAKATTAPATTRNTNKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTLDP DSYNMFENGSFLRRRRRGGGGSGGGGSGGGGSKRKKEMANKSAPEAKKKK.

[0186] A formulation can contain one or more peptides, hybrid peptides, partial peptides, or peptide fragments and said peptides can be within the vector, coupled to the vector, coupled to the DNA, or delivered by a different vector. The peptides or hybrid peptides may have one or more corresponding DNA binding sites that can bind DNA targeting sequences (DTSs) on the therapeutic nucleic acid, which bind one or more said peptide or one or more sequences on one or more peptide. For the purpose of this invention, a DTS is a sequence of DNA capable of binding a peptide sequence or a DNA binding sequence and capable of eventually promoting translocation of the DNA to the nucleus of the cell. As such, multiple coupling events between the therapeutic DNA and peptide can occur within a given formulation, multiple peptides can be coupled per strand, multiple strands can be coupled per peptide, and multiple different strands can be coupled by multiple different peptides or multiple different sites of strands and stretches of amino acids on peptides can couple together.

[0187] For the purposes of this invention capital letter symbols of amino acids and lower case letter symbols of amino acids are used interchangeably. Similarly, for the purposes of this invention capital letter symbols of DNA bases and lower case letter symbols of DNA bases are used interchangeably. It should be understood that within the scope of this invention the formulation, materials, genetic constructs, DNA and peptide sequences, biological and chemical compositions, or methods of use may be varied by one skilled in the art, to the extent that the structures described herewithin perform the desired function and remain within the scope of the present invention. Various parts, components or characteristics may be used in combination, with or without modification by someone skilled in the art to achieve the desired functionality of the af oredescribed formulation.

[0188] Moreover, all individual features and methods of use described herein, and each and every combination of two or more of such features and methods of use, are included within the scope of the present invention provided that these features and methods of use in such a combination are not mutually inconsistent. It is understood that certain portions or combinations of such portions can be varied by someone trained in the art while still achieving the main goal of the invention.

[0189] Finally, it is understood that the specific ranges provided in the current invention are not restrictive and are for example purposes only, values outside of the specified ranges may be used to achieve the goal of the invention without modification to the proposed mechanistic principals.

[0190] EXAMPLES

[0191] Example 1

[0192] In this example, a miniaturized plasmid encodes the active glucagon-like peptide 1 (GLP-1). Expression is driven by a CBh promoter, and the sequence encoding GLP-1 is followed by the bovine growth hormone (bGH) polyadenylation sequence. The construct is positioned on a null-backbone plasmid (NP) removing excess immunogenic and bacterially derived sequences. The CBh-GLP-l-bGH sequence is flanked on either side by the DNA binding motif recognized by aryl hydrocarbon receptor (AHR). A fusion peptide is produced, containing 3 identical nuclear localization sequences, then 3 identical sequences containing the DNA binding region of the AHR protein, and then 3 more nuclear localization sequences identical to the first 3. The DNA construct and fusion peptide are encapsulated in a lipid nanoparticle with an N to P ratio of 7, and at a ratio of 1 DNA binding motif to 3 peptides ( 1 miniaturized plasmid to 6 peptides ). The therapeutic is delivered by subcutaneous injection to the abdomen to treat Type 2 Diabetes Mellitus. The construct, construct sequence, and fusion peptide sequence are presented below and in FIG. 1.

[0193] FASTA Sequence (without miniaturized plasmid backbone) GGTACCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCC ATTGACGTCAATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTAC GGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGAC GTCAATGACGGTAAATGGCCCGCCTGGCATTGTGCCCAGTACATGACCTTATGGGACTTTCC TACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTCGAGGTGAGCCCCACGT TCTGCTTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTT TAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGG GCGGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCG CGCTCCGAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGC GCGCGGCGGGCGGGAGTCGCTGCGCGCTGCCTTCGCCCCGTGCCCCGCTCCGCCGCCGCCTC GCGCCGCCCGCCCCGGCTCTGACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCC CTTCTCCTCCGGGCTGTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGATGGTTGGTTGGT GGGGTATTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCACTTTTTTTCAGGTTGGGTT GCGTGCGCCACCATGGGCTGCATCATGGTGAGCATGGAGGCCAGGAGCGTGTTCGGCGTGGC CGGCGCCCTGGTGGTGGTGCTGAGCACCCTGCAGAGCGCCCAGGGCCACGGCGAGGGCACCT TCACCAGCGACGTGAGCAGCTACCTGGAGGGCCAGGCCGCCCAGGAGTTCATCGCCTGGCTG GTGGACGGCAGGTAAGTTGCGTGCCTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCC TCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGA GGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGG ACAGCAAGGGGGAGGATTGGGAAGAGAATAGCAGGCAGGCTGGGGACTAGC

[0194] CBh Promoter CGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGA CGTCAATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAA ACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAA TGACGGTAAATGGCCCGCCTGGCATTGTGCCCAGTACATGACCTTATGGGACTTTCCTACTT GGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTCGAGGTGAGCCCCACGTTCTGC TTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTAATT ATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGCGGG GCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTC CGAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCG GCGGGCGGGAGTCGCTGCGCGCTGCCTTCGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCC GCCCGCCCCGGCTCTGACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCT CCTCCGGGCTGTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGATGGTTGGTTGGTGGGGT ATTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCACTTTTTTTCAGGTTGG

[0195] GLP-1 ATGGGCTGCATCATGGTGAGCATGGAGGCCAGGAGCGTGTTCGGCGTGGCCGGCGCCCTGGT GGTGGTGCTGAGCACCCTGCAGAGCGCCCAGGGCCACGGCGAGGGCACCTTCACCAGCGACG TGAGCAGCTACCTGGAGGGCCAGGCCGCCCAGGAGTTCATCGCCTGGCTGGTGGACGGCAGG TAA

[0196] GLP-1 Protein Sequence MGCIMVSMEARSVFGVAGALVWLSTLQSAQGHGEGTFTSDVSSYLEGQAAQEFIAWLVDGR

[0197] AHR Binding Motif

[0198] GTTGCGTGC

[0199] bGH Polyadenylation Sequence CTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTG GAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAG TAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAG AGAATAGCAGGCAGGCTGGGGA

[0200] Fusion Peptide Sequence PAAKRVKLDGGGGSPAAKRVKLDGGGGSPAAKRVKLDGGGGSKSNPSKRHRDGGGGSGGGGS KSNPSKRHRDGGGGSGGGGSKSNPSKRHRDGGGGSPAAKRVKLDGGGGSPAAKRVKLDGGGG SPAAKRVKLD

[0201] NLS PAAKRVKLD

[0202] Spacers

[0203] 1) GGGGS

[0204] 2) GGGGSGGGGS

[0205] AHR DNA Binding Sequence

[0206] KSNPSKRHRD

[0207] Example 2

[0208] Naturally occurring CpG islands in the genetic constructs are utilized as the protein binding DNA sequence and are not optimized out for immunogenicity.

[0209] The DNA cassette is formulated into an LNP formulation at an N to P ratio of 7.6 and at a stoichiometric ratio of one CpG stretch (comprised of 6 CpG repeats) to one leucine rich repeat sequence such as CSTLNFTLDLSRNNLVTVQPEMFAQ. In the binding peptide, the LRR is coupled via a spacer GGGGS to a nuclear localization sequence PKKKRKV for a full peptide sequence length Of CSTLNFTLDLSRNNLVTVQPEMFAQGGGGSPKKKRKV.

[0210] The LNPs housing the DNA cassette, which contains a therapeutic protein Apelin and the DNA-binding peptide are administered subcutaneously for the treatment of sarcopenia. > Apelin MNLRLCVQALLLLWLSLTAVCGGSLMPLPDGNGLEDGNVRHLVQPRGSRNGPGPWQGGRR KFRRQRPRLSHKGPMPF

[0211] Example 3

[0212] In this example, a miniaturized plasmid encodes fibroblast growth factor 21 (FGF21 ). Expression is driven by a CBh promoter, and the sequence encoding FGF21 is followed by the bovine growth hormone (bGH) polyadenylation sequence. The CBh-FGF21-bGH sequence is flanked on either side by the DNA binding motifs recognized by CREB1, BACH1, and JDP2. A fusion peptide is produced, containing 3 different nuclear localization sequences (SOX9, MyoD, and TIMELESS Homolog), then the sequences containing the DNA binding regions of the CREB1, BACH1, and JDP2 proteins, and then 3 more nuclear localization sequences identical to the first 3. The DNA construct and fusion peptide are encapsulated in a lipid nanoparticle with an N to P ratio of 7, and at a ratio of 1 DNA binding motif to 3 peptides ( 1 miniaturized plasmid to 6 peptides ). The therapeutic is delivered by subcutaneous injection to the abdomen. The construct, construct sequence, and fusion peptide sequence are presented below and in FIG. 2.

[0213] FASTA Sequence (without miniaturized plasmid backbone) GGTACGGTGACGTCACCATGACTCATGATGACGTCATCCGTTACATAACTTACGGTAAATGG CCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAGTAACGCCAATAGGGA CTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAA GTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCA TTGTGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCA TCGCTATTACCATGGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCATCTCCCCCCCC TCCCCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTGCAGCGATGGGGGCGGG GGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAGGC GGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCGAGG CGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTCGCTGCGCGCTG CCTTCGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCCGCCCCGGCTCTGACTGACCG CGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCTGTAATTAGCTGAGC AAGAGGTAAGGGTTTAAGGGATGGTTGGTTGGTGGGGTATTAATGTTTAATTACCTGGAGCA CCTGCCTGAAATCACTTTTTTTCAGGTTGGATGGACAGCGACGAGACAGGCTTCGAGCACAG CGGCCTGTGGGTGTCCGTGCTGGCCGGCCTGCTTCTGGGCGCCTGCCAGGCCCACCCCATCC CTGATTCCAGCCCTCTGCTGCAGTTCGGCGGCCAGGTGCGGCAGCGGTACCTGTACACCGAC GACGCCCAGCAGACCGAGGCCCATCTGGAAATCAGAGAGGACGGAACAGTGGGCGGAGCTGC TGATCAGTCTCCTGAGTCCCTGCTGCAACTGAAGGCCCTGAAGCCTGGCGTGATCCAGATCC TGGGAGTGAAAACCAGCAGATTCCTGTGCCAAAGACCTGACGGCGCCCTGTACGGCTCTCTG CACTTCGACCCTGAAGCCTGTAGCTTCAGGGAACTGCTGCTGGAAGATGGATATAACGTGTA CCAGAGCGAGGCCCACGGCCTGCCTCTGCACCTGCCTGGCAACAAGTCTCCCCACCGGGACC CCGCCCCTAGAGGCCCTGCCAGATTTCTCCCACTGCCTGGACTGCCCCCCGCTCTGCCTGAG CCCCCCGGCATCCTGGCTCCACAGCCTCCAGACGTGGGCAGCTCTGATCCTCTGAGCATGGT CGGCCCCAGCCAGGGCAGAAGCCCTAGCTACGCCAGCTAACTGTGCCTTCTAGTTGCCAGCC ATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCC TTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGG GGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGAGAATAGCAGGCAGGCTGGGGA GGTGACGTCACCATGACTCATGATGACGTCATCCTAGC

[0214] FGF21 ATGGACAGCGACGAGACAGGCTTCGAGCACAGCGGCCTGTGGGTGTCCGTGCTGGCCGGCCT GCTTCTGGGCGCCTGCCAGGCCCACCCCATCCCTGATTCCAGCCCTCTGCTGCAGTTCGGCG GCCAGGTGCGGCAGCGGTACCTGTACACCGACGACGCCCAGCAGACCGAGGCCCATCTGGAA ATCAGAGAGGACGGAACAGTGGGCGGAGCTGCTGATCAGTCTCCTGAGTCCCTGCTGCAACT GAAGGCCCTGAAGCCTGGCGTGATCCAGATCCTGGGAGTGAAAACCAGCAGATTCCTGTGCC AAAGACCTGACGGCGCCCTGTACGGCTCTCTGCACTTCGACCCTGAAGCCTGTAGCTTCAGG GAACTGCTGCTGGAAGATGGATATAACGTGTACCAGAGCGAGGCCCACGGCCTGCCTCTGCA CCTGCCTGGCAACAAGTCTCCCCACCGGGACCCCGCCCCTAGAGGCCCTGCCAGATTTCTCC CACTGCCTGGACTGCCCCCCGCTCTGCCTGAGCCCCCCGGCATCCTGGCTCCACAGCCTCCA GACGTGGGCAGCTCTGATCCTCTGAGCATGGTCGGCCCCAGCCAGGGCAGAAGCCCTAGCTA CGCCAGCTAA

[0215] FGF21 Protein Sequence MDSDETGFEHSGLWVSVLAGLLLGACQAHPIPDSSPLLQFGGQVRQRYLYTDDAQQTEAHLE IREDGTVGGAADQSPESLLQLKALKPGVIQILGVKTSRFLCQRPDGALYGSLHFDPEACSFR ELLLEDGYNVYQSEAHGLPLHLPGNKSPHRDPAPRGPARFLPLPGLPPALPEPPGILAPQPP DVGSSDPLSMVGPSQGRSPSYAS

[0216] CREB1 Binding Motif

[0217] GGTGACGTCACC

[0218] BACH1 Binding Motif

[0219] ATGACTCAT

[0220] JDP2 Binding Motif

[0221] GATGACGTCATC

[0222] Fusion Peptide Sequence KRMNAFMVWAQAARRKAPELLGGPCKRKTTNADRRKAAPELLGGPGRNRAPELGAPGIQKKK RAPELLGGPRLMKNREAARECRGGGGSRRSKNRIAAQRCRKRKGGGGSRREKNKVAAARCRN KKAPELLGGPGRNRAPELGAPGIQKKKRAPELLGGPCKRKTTNADRRKAAPELLGGPKRMNA FMVWAQAARRK

[0223] Sox9 NLS

[0224] KRMNAFMVWAQAARRK

[0225] MyoD NLS

[0226] CKRKTTNADRRKA

[0227] TIMELESS Homolog NLS

[0228] GRNRAP E LGAP G I QKKKR

[0229] Spacers

[0230] 1) APELLGGP

[0231] 2) GGGGS

[0232] CREB1 DNA Binding Sequence RLMKNREAARECR

[0233] BACH1 DNA Binding Sequence

[0234] RRSKNRIAAQRCRKRK

[0235] JDP2 DNA Binding Sequence

[0236] RREKNKVAAARCRNKK

[0237] Example 4

[0238] In this example, a miniaturized plasmid contains a CBh promoter driving the expression of IGF2. The coding sequence is followed by the bovine growth hormone polyadenylation sequence. A list of proteins moderately to highly expressed in adipocytes is generated, a protein (STAT5A) selected from this list, and the recognized DNA binding motif was incorporated into the plasmid before the CBh promoter and following the polyadenylation sequence. A corresponding fusion peptide is created, incorporating the NLS and DNA Binding Sequence for STAT5A fusion peptide and plasmid are encapsulated in a lipid nanoparticle vector with an N to P ratio of 6.8 and 2 to 1 ratio of fusion peptide to plasmid.

[0239] The LNPs encapsulating the plasmid and fusion peptide are delivered subcutaneously. The construct, construct sequence, and fusion peptide sequence are presented below and in FIG. 3.

[0240] FASTA Sequence (without miniaturized plasmid backbone) GGTACTTTCTGAGAAACGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAAC GACCCCCGCCCATTGACGTCAATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGT GGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGC CCCCTATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTGTGCCCAGTACATGACCTTA TGGGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTCGAGGT GAGCCCCACGTTCTGCTTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAATTTTGTATT TATTTATTTTTTAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCCA GGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAA TCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCGGCCCTATA AAAAGCGAAGCGCGCGGCGGGCGGGAGTCGCTGCGCGCTGCCTTCGCCCCGTGCCCCGCTCC GCCGCCGCCTCGCGCCGCCCGCCCCGGCTCTGACTGACCGCGTTACTCCCACAGGTGAGCGG GCGGGACGGCCCTTCTCCTCCGGGCTGTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGAT GGTTGGTTGGTGGGGTATTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCACTTTTTTT CAGGTTGGGCCACCATGGTTTCCCCAGACCCCCAAATTATCGTGGTGGCCCCCGAGACCGAA CTCGCGTCTATGCAAGTCCAACGCACTGAGGACGGGGTAACCATTATCCAGATATTTTGGGT GGGCCGCAAAGGCGAGCTACTTAGACGCACCCCGGTGAGCTCGGCCATGCAGACACCAATGG GAATCCCAATGGGGAAGTCGATGCTGGTGCTTCTCACCTTCTTGGCCTTCGCCTCGTGCTGC ATTGCTGCTTACCGCCCCAGTGAGACCCTGTGCGGCGGGGAGCTGGTGGACACCCTCCAGTT CGTCTGTGGGGACCGCGGCTTCTACTTCAGCAGGCCCGCAAGCCGTGTGAGCCGTCGCAGCC GTGGCATCGTTGAGGAGTGCTGTTTCCGCAGCTGTGACCTGGCCCTCCTGGAGACGTACTGT GCTACCCCCGCCAAGTCCGAGAGGGACGTGTCGACCCCTCCGACCGTGCTTCCGGACAACTT CCCCAGATACCCCGTGGGCAAGTTCTTCCAATATGACACCTGGAAGCAGTCCACCCAGCGCC TGCGCAGGGGCCTGCCTGCCCTCCTGCGTGCCCGCCGGGGTCACGTGCTCGCCAAGGAGCTC GAGGCGTTCAGGGAGGCCAAACGTCACCGTCCCCTGATTGCTCTACCCACCCAAGACCCCGC CCACGGGGGCGCCCCCCCAGAGATGGCCAGCAATCGGAAGTAACTGTGCCTTCTAGTTGCCA GCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTG TCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTG GGGGGTGGGGTGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGAGAATAGCAGGCAGGCTGG GGATTTCTGAGAAACTAGC

[0241] IGF2 ATGGTTTCCCCAGACCCCCAAATTATCGTGGTGGCCCCCGAGACCGAACTCGCGTCTATGCA AGTCCAACGCACTGAGGACGGGGTAACCATTATCCAGATATTTTGGGTGGGCCGCAAAGGCG AGCTACTTAGACGCACCCCGGTGAGCTCGGCCATGCAGACACCAATGGGAATCCCAATGGGG AAGTCGATGCTGGTGCTTCTCACCTTCTTGGCCTTCGCCTCGTGCTGCATTGCTGCTTACCG CCCCAGTGAGACCCTGTGCGGCGGGGAGCTGGTGGACACCCTCCAGTTCGTCTGTGGGGACC GCGGCTTCTACTTCAGCAGGCCCGCAAGCCGTGTGAGCCGTCGCAGCCGTGGCATCGTTGAG GAGTGCTGTTTCCGCAGCTGTGACCTGGCCCTCCTGGAGACGTACTGTGCTACCCCCGCCAA GTCCGAGAGGGACGTGTCGACCCCTCCGACCGTGCTTCCGGACAACTTCCCCAGATACCCCG TGGGCAAGTTCTTCCAATATGACACCTGGAAGCAGTCCACCCAGCGCCTGCGCAGGGGCCTG CCTGCCCTCCTGCGTGCCCGCCGGGGTCACGTGCTCGCCAAGGAGCTCGAGGCGTTCAGGGA GGCCAAACGTCACCGTCCCCTGATTGCTCTACCCACCCAAGACCCCGCCCACGGGGGCGCCC CCCCAGAGATGGCCAGCAATCGGAAGTAA

[0242] IGF2 Protein Sequence

[0243] MVSPDPQI IWAPETELASMQVQRTEDGVTI IQIFWVGRKGELLRRTPVSSAMQTPMGIPMG KSMLVLLTFLAFASCCIAAYRPSETLCGGELVDTLQFVCGDRGFYFSRPASRVSRRSRGIVE ECCFRSCDLALLETYCATPAKSERDVSTPPTVLPDNFPRYPVGKFFQYDTWKQSTQRLRRGL PALLRARRGHVLAKELEAFREAKRHRPLIALPTQDPAHGGAPPEMASNRK

[0244] STAT5A Binding Motif

[0245] TTTCTGAGAAA

[0246] Fusion Peptide Sequence SQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRL VTGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEIL NNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQV KTLSLPVWIVHGSQGGGGSGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQA KSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFT VLFESQFSVGSNELVFQVKTLSLPVWIVHGSQGGGGSGGGGSKTQTKFAATVRLLVGGKLN VHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMSLKR IKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPVWIVHGSQGGGGSSQKHLQ INQTFEELRLVTGGGGSSQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVT

[0247] STAT5A NLS

[0248] SQKHLQINQTFEELRLVT

[0249] Spacers

[0250] 1) GGGGS

[0251] 2) GSAGSAAGSGEF

[0252] STAT5A DNA Binding Sequence KTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVME YHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPV WIVHGSQ Example 5

[0253] In this example, a miniaturized plasmid contains a CBh promoter driving the expression of interleukin 1 receptor antagonist (IL1RA). The coding sequence is followed by the bovine growth hormone polyadenylation sequence. The DNA binding motifs recognized by peroxisome prolif erator-activated receptor gamma (PPARG), Jun dimerization protein 2 (JDP2 ), and ALX homeobox protein 1 (ALX1 ) are incorporated on the miniaturized plasmid before the CBh promoter and following the polyadenylation sequence. A corresponding fusion peptide is created containing the NLS of parathyroid hormone related protein (PTHrP ) and the DNA Binding Sequences for PPARG, JDP2, and ALX1. The fusion peptide and plasmid are encapsulated in a lipid nanoparticle vector with an N to P ratio of 7. 4 and a 3 to 1 ratio of fusion peptide to plasmid.

[0254] The LNPs encapsulating the plasmid and fusion peptide are delivered subcutaneously for the treatment of rheumatoid arthritis. The construct, construct sequence, and fusion peptide sequence are presented below and in FIG. 4.

[0255] FASTA Sequence (without miniaturized plasmid backbone) GGTACAAGTGGGGCAAAGGTCAGATGACGTCATCTAATTAGATTACGTTACATAACTTACGG TAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTCAATAGTAACGCCA ATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCACTTGGCAGT ACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCCCG CCTGGCATTGTGCCCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACATCTACGTA TTAGTCATCGCTATTACCATGGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCATCTC CCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTAATTATTTTGTGCAGCGATGG GGGCGGGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGG GCGAGGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCCGAAAGTTTCCTTTTAT GGCGAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGCGGGAGTCGCTG CGCGCTGCCTTCGCCCCGTGCCCCGCTCCGCCGCCGCCTCGCGCCGCCCGCCCCGGCTCTGA CTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCGGGCTGTAATTA GCTGAGCAAGAGGTAAGGGTTTAAGGGATGGTTGGTTGGTGGGGTATTAATGTTTAATTACC TGGAGCACCTGCCTGAAATCACTTTTTTTCAGGTTGGATGGAAATCTGCAGAGGCCTCCGCA GTCACCTAATCACTCTCCTCCTCTTCCTGTTCCATTCAGAGACGATCTGCCGACCCTCTGGG AGAAAATCCAGCAAGATGCAAGCCTTCAGAATCTGGGATGTTAACCAGAAGACCTTCTATCT GAGGAACAACCAACTAGTTGCTGGATACTTGCAAGGACCAAATGTCAATTTAGAAGAAAAGA TAGATGTGGTACCCATTGAGCCTCATGCTCTGTTCTTGGGAATCCATGGAGGGAAGATGTGC CTGTCCTGTGTCAAGTCTGGTGATGAGACCAGACTCCAGCTGGAGGCAGTTAACATCACTGA CCTGAGCGAGAACAGAAAGCAGGACAAGCGCTTCGCCTTCATCCGCTCAGACAGTGGCCCCA CCACCAGTTTTGAGTCTGCCGCCTGCCCCGGTTGGTTCCTCTGCACAGCGATGGAAGCTGAC CAGCCCGTCAGCCTCACCAATATGCCTGACGAAGGCGTCATGGTCACCAAATTCTACTTCCA GGAGGACGAGTAGCTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCC TTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCAT CGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAAGGGG GAGGATTGGGAAGAGAATAGCAGGCAGGCTGGGGAAAGTGGGGCAAAGGTCAGATGACGTCA TCTAATTAGATTACTAGC

[0256] IL1RA ATGGAAATCTGCAGAGGCCTCCGCAGTCACCTAATCACTCTCCTCCTCTTCCTGTTCCATTC AGAGACGATCTGCCGACCCTCTGGGAGAAAATCCAGCAAGATGCAAGCCTTCAGAATCTGGG ATGTTAACCAGAAGACCTTCTATCTGAGGAACAACCAACTAGTTGCTGGATACTTGCAAGGA CCAAATGTCAATTTAGAAGAAAAGATAGATGTGGTACCCATTGAGCCTCATGCTCTGTTCTT GGGAATCCATGGAGGGAAGATGTGCCTGTCCTGTGTCAAGTCTGGTGATGAGACCAGACTCC AGCTGGAGGCAGTTAACATCACTGACCTGAGCGAGAACAGAAAGCAGGACAAGCGCTTCGCC TTCATCCGCTCAGACAGTGGCCCCACCACCAGTTTTGAGTCTGCCGCCTGCCCCGGTTGGTT CCTCTGCACAGCGATGGAAGCTGACCAGCCCGTCAGCCTCACCAATATGCCTGACGAAGGCG TCATGGTCACCAAATTCTACTTCCAGGAGGACGAGTAG

[0257] IL1RA Protein Sequence MEICRGLRSHLITLLLFLFHSETICRPSGRKSSKMQAFRIWDVNQKTFYLRNNQLVAGYLQG PNVNLEEKIDWPIEPHALFLGIHGGKMCLSCVKSGDETRLQLEAVNITDLSENRKQDKRFA FIRSDSGPTTSFESAACPGWFLCTAMEADQPVSLTNMPDEGVMVTKFYFQEDE

[0258] PPARG Binding Motif AAGTGGGGCAAAGGTCA

[0259] JDP2 Binding Motif

[0260] GATGACGTCATC

[0261] ALX1 Binding Motif

[0262] TAATTAGATTA

[0263] Fusion Peptide Sequence GKKKKGKPGKRREQRKKKRRTGGGGSGGGGSGGGGSGGGGSSGFHYGVHACEGCKGFFRRTI RLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKGGGGSGGGG SGGGGSGGGGSRREKNKVAAARCRNKKGGGGSGGGGSGGGGSGGGGSKRRHRTTFTSLQLEE LE KVF QKT H YP D V YVRE QLALRTE LTE ARVQVWF QNRRAKWRK

[0264] PTHrP NLS

[0265] GKKKKGKP GKRREQRKKKRRT

[0266] Spacer

[0267] GGGGSGGGGSGGGGSGGGGS

[0268] PPARG DNA Binding Sequence

[0269] SGFHYGVHACEGCKGFFRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAI RFGRMPQAEKEK

[0270] JDP2 DNA Binding Sequence

[0271] RREKNKVAAARCRNKK

[0272] ALX1 DNA Binding Sequence KRRHRTTFTSLQLEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRK

[0273] Example 6

[0274] In this example, a miniaturized plasmid contains a CBh promoter driving the expression of enfuvirtide. The coding sequence of enfuvirtide is preceded by the secretion signal for matrix metalloproteinase 2 (MMP2 ) and is followed by the bovine growth hormone polyadenylation sequence. The DNA binding motif for Cyclic AMP-dependent transcription factor ATF3 (ATF3 ), a spacer region, and the DNA binding motif for Forkhead box protein Cl (FOXC1 ) are inserted between the promoter and enfuvirtide, and between enfuvirtide and the polyadenylation sequence. A fusion peptide is created containing the NLS from ATP-dependent DNA helicase QI (RECQ1 ), the ATF3 DNA Binding Sequence, the FOXC1 DNA Binding Sequence, and the NLS from nucleolin, with spacers between each of the aforementioned elements. The fusion peptide and plasmid are encapsulated in a lipid nanoparticle vector with an N to P ratio of 7 and a 5 to 1 ratio of fusion peptide to plasmid.

[0275] The LNPs encapsulating the plasmid and fusion peptide are delivered subcutaneously for the treatment of HIV / AIDS. The construct, construct sequence, and fusion peptide sequence are presented below and in FIG. 5.

[0276] FASTA Sequence (without miniaturized plasmid backbone) GGTACCGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCCCCGCCC ATTGACGTCAATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTTAC GGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCCTATTGAC GTCAATGACGGTAAATGGCCCGCCTGGCATTGTGCCCAGTACATGACCTTATGGGACTTTCC TACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCATGGTCGAGGTGAGCCCCACGT TCTGCTTCACTCTCCCCATCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTT TAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGGGCGCGCGCCAGGCGGGGCGGG GCGGGGCGAGGGGCGGGGCGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCG CGCTCCGAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCGGCCCTATAAAAAGCGAAGC GCGCGGCGGGCGGGAGTCGCTGCGCGCTGCCTTCGCCCCGTGCCCCGCTCCGCCGCCGCCTC GCGCCGCCCGCCCCGGCTCTGACTGACCGCGTTACTCCCACAGGTGAGCGGGCGGGACGGCC CTTCTCCTCCGGGCTGTAATTAGCTGAGCAAGAGGTAAGGGTTTAAGGGATGGTTGGTTGGT GGGGTATTAATGTTTAATTACCTGGAGCACCTGCCTGAAATCACTTTTTTTCAGGTTGGGAT GACGTCATCCCACATATTACCTGGAAGTAAATAAACAGCCACCATGGAGGCCCTGATGGCCA GGGGCGCCCTGACCGGCCCCCTGAGGGCCCTGTGCCTGCTGGGCTGCCTGCTGAGCCACGCC GCCGCCTACACCAGCCTGATCCACAGCCTGATCGAGGAGAGCCAGAACCAGCAGGAGAAGAA CGAGCAGGAGCTGCTGGAGCTGGACAAGTGGGCCAGCCTGTGGAACTGGTTCTAAGATGACG TCATCCCACATATTACCTGGAAGTAAATAAACACTGTGCCTTCTAGTTGCCAGCCATCTGTT GTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTA ATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGG TGGGGCAGGACAGCAAGGGGGAGGATTGGGAAGAGAATAGCAGGCAGGCTGGGGACTAGC

[0277] Enfuvirtide ATGGAGGCCCTGATGGCCAGGGGCGCCCTGACCGGCCCCCTGAGGGCCCTGTGCCTGCTGGG CTGCCTGCTGAGCCACGCCGCCGCCTACACCAGCCTGATCCACAGCCTGATCGAGGAGAGCC AGAACCAGCAGGAGAAGAACGAGCAGGAGCTGCTGGAGCTGGACAAGTGGGCCAGCCTGTGG AACTGGTTCTAA

[0278] Enfuvirtide Protein Sequence MEALMARGALTGPLRALCLLGCLLSHAAAYTSLIHSLIEESQNQQEKNEQELLELDKWASLW NWF

[0279] ATF3 Binding Motif

[0280] GATGACGTCATC

[0281] FOXC1 Binding Motif

[0282] AAGTAAATAAACA

[0283] DNA Spacer

[0284] CCACATATTACCTGG

[0285] Fusion Peptide Sequence CYGSKNTGAKKRKIDDAGGGGSGGGGSGGGGSRRERNKIAAAKCRNKKRWPESPKAQASSVP TAQPQAEGSLAKATTAPATTRNTNKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTLDP DSYNMFENGSFLRRRRRGGGGSGGGGSGGGGSKRKKEMANKSAPEAKKKK

[0286] RECQ1 NLS

[0287] C YG S KNT GAKKRK I D D A Nucleolin NLS

[0288] KRKKEMANKS AP E KKKK

[0289] Spacers

[0290] 1) GGGGSGGGGSGGGGS

[0291] 2 ) RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNT

[0292] ATF3 DNA Binding Sequence

[0293] RRE RNK I AAKC RNKK

[0294] FOXC1 DNA Binding Sequence

[0295] NKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTLDPDSYNMFENGSFLRRRRR

Claims

CLAIMSWhat is claimed is:

1. A therapeutic non-viral gene delivery system for the treatment of human or veterinary pathologies comprised of:A. one or more DNA cassettes encoding one or more therapeutic transgenes or therapeutic non-coding DNA regions, and one or more protein binding stretches of DNA,B. one or more non-covalently attached peptides or hybrid peptides comprised of a nuclear localization sequence, spacer, and a DNA binding stretch of amino acid, which binds to one or more of the proteinbinding stretches from the DNA cassette.C. With an overall composition such that the stoichiometric ratio of protein binding sites to peptide molecules per non-viral gene delivery particle exceeds a critical pairing number.

2. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KRGRKP.

3. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of IRKKRGRKPLPPEQKAARRPV.

4. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of a DEXX motif.

5. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of a DEAH, DEAD, or DECH, sequence.

6. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of LXXLL motifs such as LHTLL, LHKLL, or LRYLL.

7. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of known motifs with stretches of basic amino acids.

8. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KRFARADKRGKLPR, KIEPSKPTATRKRRWSAPETRKLEKSEDEPPLTLPKPSL, PKGRQRK, or KPRRIRKPR.

9. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of a general monopartite sequence, such as K (K / R) X (K / R).

10. Nuclear localization sequence in Claim 1, which includes the motif K (K / R) X (K / R).

11. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of a general bipartite sequence, such as R / K (X) 10-12KRXK.

12. A nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of RRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEK LLAE.

13. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of EYQSAIKVEPASPP YYSEKTQLYNRPHEEPSNSLMAI.

14. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of PAAKRVKLD.

15. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of SQKHLQINQTFEELRLVT.

16. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of DEXX.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of LXXLL.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of GKKKKGKPGKRREQRKKKRRT.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KIEPSKPTATRKRRWSAPETRKLEKSEDEPPLTLPKPSL.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of RKPVTAQERQREREE KRRRRQE RAKE REKRRQERER.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of RNKKKK.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KRPACTLKPECVQQLLVCSQEAKK.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of PKKKRKV.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of CYGSKNTGAKKRKIDDA.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of RKKRRQRRR.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of RQARRNRRRRWR.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KRMNAFMVWAQAARRK.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KARTPIQKHWRPTVLTEGPPVKIRETGEWEKA.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KRPAATKKAGQAKKK.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KRKKEMANKSAPEAKKKK.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of APTKRKGS.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KQRDAEHRDRTKKKKRSRSRDRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNK VKSRYRSRSRSQSPPKDRKDRDK.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of MSDYGTAR.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of PRRTTRRHPNTQQRASKKKPK.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of GRNRAPELGAPGIQKKKR.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of KLGPRKATGRW.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of PAKRPRETPSPADPPGGASKPRK.Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of RLNDAI IKRHVLVLSE YADLKYLGFEKYKFFE Y.

39. Nuclear localization sequence in Claim 1, which is comprised at least in part from at least a part of RRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEK LLAE, EYQSAIKVEPASPPYYSEKTQLYNRPHEEPSNSLMAI, PAAKRVKLD, SQKHLQINQTFEELRLVT, SQKHLQINQTFEELRLVT, SQKHLQINQRFEELRLIT, DEXX, DEAH, DEAD, DECH, LXXLL, LHTLL, LHKLL, LRYLL, KRFARADKRGKLPR, KIEPSKPTATRKRRWSAPETRKLEKSEDEPPLTLPKPSL, PKGRQRK, KPRRIRKPR, PKPS, SKL, PKKKRKV, K (K / R) X (K / R), PKLKRQ, RPRK, RRARRPRG, R / K (X) 10-12KRXK, GKRKLITSEEERSPAKRGRKS, KGKKGRTQKEKKAARARSKGKN, KRCAAGVGGGPAGCPAPGSTPLKKPRR, RKPVTAQERQREREE KRRRRQE RAKE REKRRQERER, RSGGNHRRNGRGGRGGYNRRNNGYHPY, TLLLRETMNNLGVSDHAVLSRKTPQP Y, P GKMDKGEHRQERRDRP Y, GKKKKGKP GKRREQRKKKRRT,S ANKVTKNKSNS SP YLNKRKGKP GP D S, VHSHKKKKIPTSPTFTTPKTLTLRRQPKYPRKSAPRRNKLDHY, RKHKTNRKPR, NRRAKAKR, RNKKKK, RKVIK, Rrmkwkk, Rvhpyqr, Krpactlkpecvqqllvcsqeakk, Pkkkrkv, gkkrska, kakrqr, rgrrrrqr, rkrrr, ppvkrerts, pylnkrkgkp, cygskntgakkrkidda, kkkkrkrek, kkkrrsrek, rkriredrkx- (18) rkrkr, rrerx ( 4 ) rprkipr, kkkkkeeegegkkk, prprkipr, ppriypqlpsapt, kdcvinkhhrnrcqycrlqr, krx (9) ktkk, apkrksgvskc, rkkrrqrrr, rqarrnrrrrwr, mpktrrrprrsqrkrppt, krpmnaf ivwsrdqrrk, prrk, krmnafmvwaqaarrk, prrrk, kartpiqkhwrptvltegppvkiretgeweka, pprkkrtvv, ykrpckrsf irf i, Ikdvrkrklgpgh, rkprp, rkrkkkraaeddedddvdtkkqk, grkrkkrt, kkkqkk, rekkekeqkekca, lekkvkkkf dwca, tekkqgksilydca, sdkkvrsrlieca, Ikrklqr, rrkgkek, ckrkttnadrrka, vneafetlkrc, mpteervrkrkesnresarrsryrkaahlk, kvnsrkrrkevpgpngateed, prrgpr, prgrrqpipkarqp, krsaeggnppkplkklr,krkx (11) kkkskk, eylsrkgklel, pkrprdrhdgelggrkrarg, krpaatkkagqakkk, krkkemanksapeakkkk,rkrafhgddpf gegppddkk, gggx (3) knrrx (6) rggrn,ynnqssnf gpmkggn, paakrvkld, krpaedmeeeqaf krsr, sxgtkrsyxxm, mnkipkdllnpg, pkkared, vsrkrpr, aptkrkgs, pnkkkrk, eedgpqkkkrrl, pllkkikq, ppqkkiks, pqpkkkp, skrvakrkl, ikyfkkfpkd, ktrkhrg, khrkhpg, pqsrkklr, hrkyeaprhx ( 6) prkr, kkekkkskk, QRDAEHRDRTKKKKRSRSRDRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNKV KSRYRSRSRSQSPPKDRKDRDK, RDRTKKKKRSRSRDRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNKVKSRYRS RSRSQSPPKDRKDRDKY, KKRIR, KRKYR, PKRRK, KRRP, KKKLKK, MSDYGTAR, IEWESVLT, QKDSDSKL, KKGKDEWF, MMPNKVRKIGELVRYLNTNPVGGLLEYARSHGFAAEFKLVDQSGPPHEPKFVYQAKV GGRWFPAVCAHSKKQGKQEAADAALRVLIGENEKAER, LKRQQRMIKNRESACQSRRKKKEYLQGLEARLQAVLADNQQLRRENAALRRRLEALL AENSEL, VLRRQQRMIKNRESACQSRKKKKEYMLGLEARLKAALSENEQLKKENGTLKRQLDEV VSENQRL, PRRTTRRHPNTQQRASKKKPK, KKRK, NSLLVPDSLRGTDKRRNGPEFSNDIKKRKVDDKDSSHYDSDGDKSDDNLWDVSNED PSSPRASPAHSP, KQRA, ASPSPPESLVEEERPSGPGGGGKQRADEKEPSGPYESDEDKSDYNLWDEDQPSEPP SPATTP, KKRK, NSVSPSESLRASEKHRGSADYSMEAKKRKAEEKDSLSRYDSDGDKSDDLWDVSNED PATPRVSPAHSP, SSVSPSASFRGAEKHRNSADYSSESKKQKTEEKEIAARYDSDGEKSDDNLWDVSNE DPSSPRGSPAHSP, RRMKWKK, GSRKR, KQKQRFEEKRFK, GAVAED, GRNRAP E LGAP G I QKKKR,ECTRGGFCNFMHLRP I SQNLQRQLYGRGPRRRSPPRFHTGHHPRERNHRCSPDHWHG RF, KGPRAKVAKLNIQSLSPVKKKKMVPGALGVPADLAPVDVEFSFPKFSRLRRGLKAEA VKGPVPAAPARRRLQL, PRLRVR, KVKTKKSTK, RGPEPARETPAKLEPKPIIPKAEPRAKARKTEARGLTKAGAKKKARK, PAKLEPKPIIPKAEPRAKARKTEARGLTKAGAKKKARKE, KKRPSR, and KKR.

40. Spacer in Claim 1, which is comprised at least in part from at least a part of a peptide bond to up to 42 amino acids.

41. Spacer in Claim 1, which is comprised at least in part from at least a part of a disordered stretch of amino acids 6 to 42 amino acids in length.

42. Spacer in Claim 1, which is comprised at least in part from at least a part of a disordered stretch of amino acids 6 to 36 amino acids in length.

43. Spacer in Claim 1, which is comprised at least in part from at least a part of a disordered stretch of amino acids 6 to 32 amino acids in length.

44. Spacer in Claim 1, which is comprised at least in part from at least a part of a disordered stretch of amino acids 6 to 26 amino acids in length.

45. Spacer in Claim 1, which is comprised at least in part from a disordered domain rich in one or more of glycine, serine, proline, glutamine, asparagine, lysine, arginine, glutamic acid, or aspartic acid.

46. Spacer in Claim 1, which is comprised at least in part from at least a part of KSKSSSSSSSSTSS.

47. Spacer in Claim 1, which is comprised at least in part from at least a part of LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES, AKKSKTAAKKNDKEAAG, RNSSKCKSKPQIAALKEETEEEVQDTRL, SSKAPPPSLPSPSRLPG, GRDELGGGRRPGTSPALLQGTAE, AKAEAGAEAGGGAGPGAEDEAGRGAVGDPELGDPPAAPQ, EASQSHLRN, KKIKGIQQATTGVSQETSENPGNKTIVPATLPQ, DEKTEESDTDRLLSSDHEKSHSNLGV, AGEGGPP, HEXXHXXG, NEXXSD, GX5EX7REUXEEXGU U = bulky hydrophobic, PVPSTPPTPSPSTPPTPSPSC, PVPX ( 1-12 ) PPPPC, EPKSCDKTHT, CPPCP, APELLGGP, ERK, CCVECPPCP, APPVAXGP, ELKTPLGDTTHT, CPRCP, EPKSCDTPPPCPRCP, APELLGGP, ESKYGX ( 1-5 ) PP, CPSCP, AP E F LGGP, RWP ESP KAQAS SVP T AQP QAE G S LAKAT T AP AT TRNT, GTELSVKPNLNKVFPPEV, HXXG, AEEHTDLEAQ, HXXXH, SDQEAKPSTEDLG, QTGGHSTV, GGGGS, GGGGSGGGGS,GGGGSGGGGSGGGGS, GSAGSAAGSGEF, HHHH, and GGGGSGGGGSGGGGSGGGGS.

48. Spacer in Claim 1, which is derived from proteins with high disorder propensity.

49. Spacer in Claim 1, which is derived predominantly from proteins with high disorder propensity.

50. Spacer in Claim 1, which is derived from an amino acid stretch where at least half of the amino acids in a spacer sequence are derived from amino acids with disorder propensity of 0.4 or greater.

51. Spacer in Claim 1, which is derived from an amino acid stretch where at least half of the amino acids in the spacer sequence are derived from amino acids with disorder propensity of 0.43 or greater.

52. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part of a protein that contains a DNA-binding region.

53. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part Of RREKNKVAAARCRNKK.

54. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part of NKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTLDPDSYNMFENGSFLRRRRR.

55. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part of a protein that is moderately to highly expressed in adipocytes and that contains a DNA-binding region.

56. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part ofSGFHYGVHACEGCKGFFRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGM SHNAIRFGRMPQAEKEK.

57. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part Of NHN I LE RQRRND LRSSFLTLRD H VP E LVKNE KAAK.

58. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part Of KSNPSKRHRD.

59. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part Of RERNNIAVRKSR.

60. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part of KRRHRTTFTSLQLEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRK.

61. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part Of RRSKNRIAAQRCRKRK.

62. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part of KTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNN CCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELV FQVKTLSLPVWIVHGSQ.

63. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part Of RGNVTSLSLSSNRIHHLHDSDFAH, RGNVTSLSLSSNRIHHLHDSDFAHLPSLRHLNLKWNCPPVGLSPMHFPC, HLPSLRHLNLKWNCPPVGLSPMHFPC, VPTLEELNLSYNNIMTVPALPKSLISLSLSHTNILMLDSASLAGLHALRFLFMDGNC YYKNPCRQALEV, LGNLTHLSLKYNNLTWPRNLPSS, LGNLTHLSLKYNNLTWPRNLPSSLEYLLLSYNRIVKLAPEDLANLTALRVLDVGGN CRRCDHAPNPCMEC, LSRLEGLVLKDSSLSWLNASWFRGLGNLRVLDLSENFLYKCITKTKAFQGLTQLRKL NLSFNYQKRVSFAHLSL,LVALKELDMHGIFFRSLDETTLRPLARLPMLQTLRLQMNFINQAQLGIFRAFPGLRY VDLSDNRISGASELTATMGEA, CSTLNFTLDLSRNNLVTVQPEMFAQLSHLQCLRLSHNCISQAVNGSQFLPLTGLQVL DLSHNKLDLYHEHSFTELPRLEALDLSYNSQPFGMQGVGHNFSFVAHLRTLRHLSLA HNNIHSQVSQQLCSTSLRALDFSGNALGHMWAEGDLYLH, LSGLIWLDLSQNRLHTLLPQTLRNLPKSLQVLRLRDNYLAFFKWWSLHFLPKLEVLD LAGNQLKALTNGSLPAGTRLRRLDVSCNSISFVAPGFFS, xLxxLxLxxNxLxxLPxxxFx,GFHYGVHACEGCKGFFRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMS HNAIRFGRMPQAEKEK, SGFHYGVHACEGCKGFFRRTIRMKLEYEKCERSCKIQKKNRNKCQYCRFQKCLALGM S HNAI RF GRMP E AE K, SGYHYGVHACEGCKGFFRRTIRLKLVYDKCDRSCKIQKKNRNKCQYCRFHKCLSVGM SHNAIRFGRMPRSEKAKLKAEILTCEHDIEDSETADLKSLAKR, SGYHYGVSACEGCKGFFRRSIQKNMI YTCHRDKNCVINKVTRNRCQYCRLQKCFEVG MSKESVRNDRNKKKKETSKQECTESYEMTAELDDLTEKIRKAHQETFPSLCQLGKYT TNSSADHRVR,SGYHYGVSACEGCKGFFRRSIQKNMVYTCHRDKNCI INKVTRNRCQYCRLQKCFEVG MS KE S VRND RNKKKKE V, SGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCI INKVTRNRCQYCRLQKCFEVG MS KE AVRNDRNKKKKVKEEGSPDSYE, SGKHYGVYSCEGCKGFFKRTIRKDLI YTCRDNKDCLIDKRQRNRCQYCRYQKCLVMG MKREAVQEERQRSRERA, SGKHYGVYSCEGCKGFFKRTVRKDLTYTCRDNKDCLIDKRQRNRCQYCRYQKCLAMG MKREAVQEERQRGKDRN, SGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKKCLSV GMSRDAVRFGRIPKREKQ, SGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCVMDMYMRRKCQECRLRKCKEMG MLAECMYTGLLTEIQCKSKRLRKNVKQHADQTVNEDSEGRDLRQVTSTTKSCREKTE LTPDQQTLLHFIMDSYNKQRMPQEITNKILKEELSAEENFLILTEMATNHVQVLVEF TKKLPGFQTLDHEDQIALLKGSAVEAMFLRSAEIFNKKLPSGHSDLLEER, SGYHYNALTCEGCKGFFRRSITKNAVYKCKNGGNCVMDMYMRRKCQECRLRKCKEMG MLAECMYTGLLTEIQCKSKRLRKNVKQHADQTVNEDSEGRDLR,SGFHYNVLSCEGCKGFFRRSWRGGARRYACRGGGTCQMDAFMRRKCQQCRLRKCKEAGMREQCVLSEEQIRKKKIRKQQQESQSQSQSPVGPQGS, SGFHYGVHACEGCKGFFRRSIQQNIQYKRCLKNENCSIVRINRNRCQQCRFKKCLSV GMS RDAVRF GRIP, SGKHYGQFTCEGCKSFFKRSVRRNLTYTCRANRNCPIDQHHRNQCQYCRLKKCLKVG MRREAVQRGRMP, SGKHYGQFTCEGCKSFFKRSVRRNLSYTCRANRNCPIDQHHRNQCQYCRLKKCLKVG MRREAVQRGRMP, SGFHYGVHACEGCKGFFRRSIQQNIQYKKCLKNENCSIMRMNRNRCQQCRFKKCLSV GMS RDAVRF GR I PKREKQ, SGIHYGVITCEGCKGFFRRSQQNNASYSCPRQRNCLIDRTNRNRCQHCRLQKCLALG MSRDAVKFGRMSKKQ, SGIHYGVITCEGCKGFFRRSQQSNATYSCPRQKNCLIDRTSRNRCQHCRLQKCLAVG MSRDAVKFGRMSKKQR, SGIHYGVITCEGCKGFFRRSQRCNAAYSCTRQQNCPIDRTSRNRCQHCRLQKCLALG MSRDAVKFGR, KVKWTHEEDEQLRALVRQFGQQDWKFLASHFPNRTDQQCQYRWLRVLNPDLVKGPWT KEEDQKVIELVKKYGTKQWTLIAKHLKGRLGKQCRERWHNHLNPEVKKSCWTEEEDRIICEAHKVLGNRWAEIAKMЛPGRTDNAVKNHWNSTIKR, KTRWTREEDEKLKKLVEQNGTDDWKVIANYLPNRTDVQCQHRWQKVLNPELIKGPWT KEEDQRVIELVQKYGPKRWSVIAKHLKGRIGKQCRERWHNHLNPEVKKTSWTEEEDRIIYQAHKRLGNRWAEIAKLLPGRTDNAIKNHWNSTMRR, DKGKEKPTDMQNFGLRTDMYTKKNVPSKSKAAASATREWTEQETLLLLEALEMYKDD WNKVSEHVGSRTQDECILHFLR,RL AANARE RRRMHGLNHAFD Q LRNV IPSFNNDKKLSK, PHRLIEKKRRDRINECIAQLKDLLPEHLKLTTLGHL, NHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAK, KSNPSKRHRD, RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASR, RNAANARERARM, RLKINSRERKRM, RLMKNREAARECR, RRERNKIAAAKCRNKK, RKLKNRVAAQTARDRK, RYKNNEAAKRSR, RRRKNNMAAKRSR, RERNNIAVRKSR, RKIKNKI SAQESR, RREKNKVAAARCRNKK,RRE KNR I AAQKS RQRQ,KKRGIFPKVATNIMRAWLFQHLTHP YPSEEQKKQLAQDTGLTILQVNNWFINARRR, KRKRRGNLPKESVKILRDWLYLHRYNAYPSEQEKLSLSGQTNLSVLQICNWFINARRR,PKRPRTILTTQQRRAFKASFEVSSKPCRKVRETLAAETGLSVRWQVWFQNQRAKMK K, RSIWDGEETSYCFKEKSRSVLREWYAHNPYPSPREKRELAEATGLTTTQVSNWFKNR RQRDRA, TKRRGPRTTIKAKQLETLKAAFAATPKPTRHIREQLAQETGLNMRVIQVWFQNRRSK ERRMKQLSALGAR, KRRHRTTFTSLQLEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRK,SQGSVSE I LARPKP WRKLTVKGKEPF I KMKQFLSDEQNVLALRT I QVRQRGS I TPRI RTPETGSDDAIKSILEQAKKEIESQKGGEPKTSVAPLSIANGTTPASTSEDAIKSIL E QARREMQAQQQALLEME VAP RGRSVPPSPPERPS LAT AS QNGAP ALVKQE E G S GGP AQAPLPVLSPAAFVQSI IRKVKSEIGDAGYFDHHWASDRGLLSRP YASVSPSLSSSS SSGYSGQPNGRAWPRGDEAPVPPEDEAAAGAEDEPPRTGELKAEGATAEAGARLPYY PAYVPRTLKPTVPPLTPEQYELYMYREVDTLELTRQVKEKLAKNGICQRIFGEKVLG LSQGSVSDMLSRPKPWSKLTQKGREPFIRMQLWLSDQLGQAVGQQPGASQASPTEPR SSPSPPPSPTEPEKSSQEPLSLSLESSKENQQPEGRSSSSLSGKMYSGSQAPGGIQE IVAMSPELDTYSITKRVKEVLTDNNLGQRLFGESILGLTQGSVSDLLSRPKPWHKLS LKGREPFVRMQLWLNDPHNVEKLRDMKKLEKKAYLKRRYGLISTGSDSESPATRSEC PSPCLQPQDLSLLQIKKPRWLAPEEKEALRKAYQLEP YPSQQTIELLSFQLNLKTN TVI NWF HN YRSRMRR,KNKRGVLPKHATNIMRSWLFQHLMHP YPTEDEKRQIAAQTNLTLLQVNNWFINARRR, GWKNSIRHNLSLNKCFRKVPRPRDDPGK, SSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWI INPDGGKSGKAPRR, AWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTLDPQSEDMFDNGSFLRRRKR, RPEKPP YSYIALIVMAIQSSPSKRLTLSEI YQFLQARFPFFRGAYQGWKNSVRHNLS LNECFIKLPKGLGRPGKGHYWTIDPASEFMFEEGSFRRRPR, NKQGWQNSIRHNLSLNECFVKVPRDDKKPGKGSYWTLDPDSYNMFENGSFLRRRRR, HTASPWNLSPFSKTSIHHGSPGPLSVYPPASSSSLSGGHASPHLFTFPPTPPKDVSP DPSLSTPGSAGSARQDEKECLKYQVPLPDSMKLESSHSRGSMTALGGASSSTHHPIT TYPPYVPEYSSGLFPPSSLLGGSPTGFGCKSRPKARSSTGRECVNCGATSTPLWRRD GTGHYLCNACGLYHKMNGQNRPLIKPKRRLSAARRAGTSCANCQTTTTTLWRRNANG DPVCNACGLYYKLHNINRPLTMKKEGIQTRNRK, PLWRRDGTGHYLCNACGLYHKMNGQNRPLIKPTSCANCQTTTTTLWRRNANGDPVCN ACGLYYKLHNINRPLTMKKEGIQTRNRKM,PLWRRDGTGHYLCNACGLYSKMNGLSRPLIKPQKRVPSSRRLGLSCANCHTTTTTLW RRNAEGEPVCNACGLYMKLHGVPRPLAMKKEGIQTRKRK, VEEEISRHYRRAHSCYKCRQCSFTAADTQSLLEHFNTVHCQEQDITTANGEEDGHAI STIKEEPKIDFRVYNLLTPDSKMGEPVSESWKREKLEEKDGLKEKVWTESSSDDLR NVTWRGAD I LRGSP S YTQASLGLLTP VSGTQEQTKTLRD SPNVEAAHLARP I YGLAV ETKGFLQGAPAGGEKSGALPQQYPASGENKSKDESQSLLRRRRGSGVFCANCLTTKT SLWRKNANGGYVCNACGLYQKLHSTPRPLNI IKQNNGEQI IRRRTRKRLNPEALQAE QLNKQQRGSNEEQVNGSPLERRSEDHLTESHQREIPLPSLSKYEAQGSLTKSHSAQQ PVLVSQTLDIHKRMQPLHIQIKSPQESTGDPGNSSSVSEGKGSSERGSPIEKYMRPA KHPNYSPPGSPIEKYQYPLFGLPFVHNDFQSEADWLRFWSKYKLSVPGNPHYLSHVP GLPNPCQNYVP YPTFNLPPHFSAVGSDNDIPLDLAIKHSRPGPTANGASKEKTKAPP NVKNEGPLNWKTEKVDRSTQDELSTKCVHCGIVFLDEVMYALHMSCHGDSGPFQCS ICQHLCTDKYDFTTHIQR, QEGRLQRKQKNATGGRRHICHECGKSFAQSSGLSKHRRIHTGEKP YECEECGKAFIG SSALVIHQRVHTGEKP YECEECGKAFSHSSDLIKHQRTHTGEKP YECDDCGKTFSQS CSLLEHHRIHTGEKP YQCSMCGKAFRRSSHLLRHQRIHTGDKNVQEPEQGEAWKSRM ESQLENVETPMSYKCNECERSFTQNTGLIEHQKIHTGEKPYQCNACGKGFTRISYLV QHQRS, REAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDK, KSNPSKRHRD, RENHSEIERRRRNKMTAYITELSDMVPTCPDK, RGMRFRYECEGRSAGSILGESSTEASKTLPAIELRDCGGLREVEVTACLVWKDWPHR VHPHSLVGKDCTDGICRVRLRPHVSPRHSFNNLGIQCVRKKEIEAAIERKIQLGIDP YNAGSLKNHQEVDMNWRICFQASYRDQQGQMRRMDPVLSEPVYDKKSTNTSELRIC RINKESGPCTGGEELYLLCDKVQKEDISWFSRASWEGRADFSQADVHR, MSSAIERKSLDPSEEPVDEVLQIPPSLLTCGGCQQNIGDRYFLKAIDQYWHEDCLSC DLCGCRLGEVGRRLYYKLGRKLCRRDYLRLFGQDGLCASCDKRIRAYEMTMRVKDKV YHLECFKCAACQKHFCVGDRYLLINSDIVCEQDIYEWTKINGMI, KRPRTTITAKQLETLKSAYNTSPKPARHVREQLSSETGLDMRWQVWFQNRRAKEKRr PKRPRTILTTQQRRAFKASFEVSSKPCRKVRETLAAETGLSVRWQVWFQNQRAKMKK, NGRPLPDWRQRIVELAHQGVRPCDISRQLRVSHGCVSKILGRYYETGSIKPGVIGG S KP KVATP KWE K I AE YKRQNP TMF AWE I RD RLLAE RVCDND T VP SVSSINRIIR, NGRPLPNAIRLRIVELAQLGIRPCDISRQLRVSHGCVSKILARYNETGSILPGAIGG SKPRVTTPTWKHIRTYKQRDPGIFAWEIRDRLLADGVCDKYNVPSVSSISRILR,KYFKKHEKR, DGRLQVAGRKGFPHVI YARLWRWPDLHKNELKHVKYCQY, DGRLQVSHRK, RRMFPTIRVSFSGVDPEAKYIVLMDIVPVDNKRYRYAYHRSSWLVAGKADPPLPARL YVHPDSPFTGEQLLKQMVSFEKVKLTNNELDQHGHI ILNSMHKYQPRVHI IKKKDHT ASLLNLKSEEFRTFIFPETVFTAVTAYQNQLITKLKIDSNPFAKGF, LTTEADSGY, AYRQK, HFARKDLSEADARIFKAWAVARGRWPPSSRGGGPPPEAETAERAGWKTNFRCALRS, RRSKNRIAAQRCRKRK, LHVENYLRHLKMHKLFLCLQCGKTFTQKKNLNRHIRGHMGIRPFQCTVCLKTFTAKS TLQDHLNIHSGDRPYKCHCCDMDFKHKSALKKHLTS, andEKLSRGLRY Y YDKNI I HKTAGKR.

64. A DNA binding stretch of amino acids in Claim 1, which is comprised at least in part from at least a part of eenvkRrTHNvLErqRRnelkr,eenvkRrTHNvLERqRRNelkRsff alrdqipelennekapKvvilk, mnvkRrtHNvLERqRRNelkRsff alrdqipelennekapKvvilk, hmnvkRrtHNvLERqRRNelkRsff alrdqipelennekapKvvilk, serrrNHNiLErqRRndlRssf It IrdhvpelvknekaaKvvilk, tkkkyHSyLErkRRndqRsrf lalrdevpalascsrVsKvmilv, saadkRaHHNaLErkRRdhiKdsfhslrdsvpslqgekasRaqild, errrvRRerNKlAAakCRnrrkeltdf IqaetdkledeksglqreiEelqkq, ekrriRRerNKlAAakCRnrRrelte, ekrriRRerNKmAAakCRnrRreltd, krriRRerNKmAAakSRnrrre,cgdkaSGf HYgvhacEGcKGf fRRtirlkliydrcdlncrihkksrNkcqyc, cgdkaSGf HYgvhacEGcKGf fRRtirmkleyekcersckiqkknrNkcqyc, cgdkaSGy HYgvhacEGcKGf fRRtirlklvydkcdrsckiqkknrNkcqyc, scgslNmecrvcgdKaSGFHYgvhacEGcKGf fRRtirmkleyekcersckiqkknr Nkcqyc, qarkaFnckycnkeyLSLGAlKMhIRsht Ip,cnktySTf SGlaKhkqLhcdaq,ppqvlKtqtkf aatvrllvggklnvhmnppqvkatiiseqqaksllknentrnecsg eilnncc,meyhqatgtlsahf rnmslkrikradrrgaEsvteekftvlf esqf svgsnelvf qv ktlslp, vvviVHGSQdhnat,ppqvlKtqtkfaatvrllvggklnvhmnppqvkatiiseqqaksllknentrndysgeilnncc,meyhqatgtlsahf rnmslkrikr sdrrgaEsvteekf til f esqf svggnelvfqv kt 1 s Ipvvvi VHGSQdnnat,ppqvlKtqtkf qagvrf llglrf Igapakpplvradmvtekqarelsvpqgpgagae stgeiin,tvpl ensipgncc salt knlllkkikrcerkgtEsvteekcavlf sasftlgpgklp iqlqal, slplvviVHGNQdnnak,ppqvlKtqtkf qagvrf llglrf Ipakpplvradmvt ekqarele st gei innt vpl ensipgn,csalf knlllkkikrcerkgtEsvteekcavlf sas ft Igpgklpiqlqalslplvv iVHGNQdnnak,ppqvlKtqtkf qagvrf llglrf pakpplvradmvt ekqarele st gei innt vple nsipgnc,salf knlllkkikrcEgtesvteekcavlf sasftlgpgklpiqlqalslplvviVH GNQdnnak,ppqvlKtqtkf qagvrf llglrf Igpakpplvradmvt ekqaret gei innt vplen sipgncc,salf knlllkkikrcerkgtEsvteekcavlf sas ft IglpiqlqalslplvviVHG NQdnnak,ppqvlKtqtkf qagvrf llglrf Igapakpplvradmvt ekqaret gei innt vple nsipgnc,salf knlllkkikrcerkgtEsvteekcavlf sas ft IgppiqlqalslplvviVHG NQdnnak,ppqvlKtqtkf qagvrf llglrf Igapakpplvradmvt ekqaret gei innt vple nsipgnc,csalf knlllkkikrcEgtesvteekcavlf sas ft IgpiqlqalslplvviVHGNQ dnnak, ItkteHpkSsf rlhRMrrMgsasr, chkmySNKGTIRVhyktv, neyrvRRerNNiAVrkSRdkakq, leyrlRReRNNiAVrKSRdkakr, eyrlrRerNNiAVrkSRdkakr, eykirRerNNiAVrkSRdkakm, ssgprTrklkk,kpkkkNpnkeDKRPRtaftaeqlqrlkaef qtnrylteqrrqslaqelslneSQiKI wfQNkrAKikKatgnk,dldrpKRTRt sftaeqlyrlemef qrcqyvvgrertelarqlnlseTQvKVWfQNRr TKqkKdqgkd,dldrpKRTRt sftaeqlyrlemef qrcqyvvgrertelarqlnlseTQvKVwfQNrr TKqkKdqsrd,IhcrrKRRHRtiftdeqlealenlf qetkypdvgtreqlarkvhlreEKvEVwfKNr rAKwrRqkrss,pgsqrRtRRHRtif seeqlqalealfvqnqypdvstrerlagrirlreERvEVwfKN rrAKwrHqkras,harstRKKRcpytkyqtlelekef If nmyltrdrryevarvlnlteRQvKIwfQNrr MKmkKmnkek,harssRKKRcpytkyqtlelekef If nmyltrdrrhevarllnlseRQvKIwfQNrr MKMkKmnkeq,harstRKKRcpytkhqtlelekef If nmyltrdrryevarllnlteRQvKIwfQNrr MKMkKinkdr,harssRKKRcpytkyqtlelekef If nmyltrdrrhevarllnlseRQvKIwfQNrr MKMkKmnkeq,harstRKKRcpytkyqtlelekef If nmyltrdrryevarilnlteRQvKIwfQNrr mkm,taksgRKKRcpytkhqtlelekef If nmyltrerrleisktinltdRQvKIwfQNrr MKlkKmnren, ekeskEeiksd,taksgRKKRcpytkhqtlelekef If nmyltrerrleisrsvhltdRQvKIwfQNrr MKlkKmnren, IgsgqRqsASeREklRMrt lar, paggqRqsASeREKIRMrtlar, msvqrRrkaSeREklRMrtlad, ikktrRlkANnRERnRMhnlnaaldalrevlpt fpedakltKietlr, itkagRrmfpamrvkisgldphqqyyiamdivpvdnkryryvyhsskwmvagnadsp vpprvyi,pdspasgetwmrqvisf dklkltnnelddqghiilhsmhkyqprvhvirkdcgddls pikpvpsgegvkaf sfpetvfttVTAyqnqqitrlkidrnpFakGFrdsgr, itkagRrmfpamrvkitgldphqqyyiamdivpvdnkryryvyhsskwmvagnadsp vpprvyihpdslasgdtwmrqvvSf dKLkltnnelddqghiilhsmhkyqprvhvir kdf ssdlsptkpvpvgdgvkt f nfpetvfttvTAyqnqqitrlkidrnpFakGFrds gr, itkagRrmfpamrvkisgldphqqyyiamdivpvdnkryryvyhsskwmvagnadsp vpprvyihpdspasgetwmrqvisf dklkltnnelddqghiilhsmhkyqprvhvir kdcgddlspikpvpsgegvkaf sfpetvfttvTAyqnqqitrlkidrnpFakGFrds gr,itkagRrmfpamrvkitgldphqqyyiamdivpvdnkryryvyhsskwmvagnadsp vpprvyihpdslasgdtwmrqvvSf dKLkltnnelddqghiilhsmhkyqprvhvir kdf ssdlsptkpvpvgdgvkt f nfpetvfttvTAyqnqqitrlkidrnpFakGFrds gr,itksgRrmfptirvsf sgvdpeakyivlmdivpvdnkryryayhrsswlvagkadpp Iparlyvhpdspftgeqllkqmvsf ekvkltnneldqhghiilnsmhkyqprvhiik kkdhtasllnlkseef rt f ifpetvftavTAyqnqlitklKidsnpFakGFrdssr, vtkagRrmfpt f qvklf gmdpmadymllmdfvpvddkryryafhssswlvagkadpa tpgrvhyhpdspakgaqwmkqivsf dklkltnnllddnghiilnsmhryqprfhvvy vdprkdsekyaeenf kt fvf eetrftavTAyqnhritqlkiasnpFakGF, vtkagRrmfpt f qvklf gmdpmadymllmdfvpvddkryryafhssswlvagkadpa tpgrvhyhpdspakgaqwmkqivsf dklkltnnllddn ghiilnsmhryqprf hwy vdprenf kt fvf eetrftavTAyqnhritqlkiasnpFakGF, or vtkagRrmfpt f qvklf gmdpmadymllmdfvpvddkryryafhssswlvagkadpa tpgrvhyhpdspakgaqwmkqivsf dklkltnnllddn ghiilnsmhryqprf hwy vdprkdsekyaeenf kt fvf eetrftavTAyqnhritqlkiasnpFakGFrdcdp.

65. A DNA binding stretch of amino acids in Claim 1, which is derived at least in part from at least a part of the following protein domain sequences: C2H2 type zinc finger, Zinc finger, C2H2 type, Zinc finger double domain, C2H2 type zinc finger, Homeobox domain, Myb like DNA binding domain, Helix loop helix DNA binding domain, Zinc finger, C4 type (two domains), Myb like DNA binding domain, bZIP transcription factor, Basic region leucine zipper, Ligand binding domain of nuclear hormone receptor, Zinc finger of C2H2 type, Homeobox KN domain, HMG (high mobility group) box, Domain of unknown function (DUF1898), Fork head domain, Ets domain, AP2 domain, GATA zinc finger, Pou domain N terminal to homeobox domain, KRAB box, Fungal Zn (2) Cys (6) binuclear cluster domain, Ankyrin repeat, PAS fold, Rel homology domain (RHD), GTF2I like repeat, LIM domain, C2H2 type zinc finger domain, ' Paired box' domain, MH1 domain, SRF type transcription factor (DNA binding and dimerizationdomain), AT hook motif, T box, IPT / TIG domain, Ankyrin repeats (3 copies), Interferon regulatory factor transcription factor, BTB / POZ domain, Sterile alpha motif (SAM) / Pointed domain, No apical meristem (NAM) protein, PAS fold, CUT domain, WRKY DNA binding domain, bZIP Maf transcription factor, Fungal specific transcription factor domain, B3 DNA binding domain, Sigma 70, region 4, E2F / DP family winged helix DNA binding domain, Interferon regulatory factor 3, N terminal CTNNB1 binding, Sigma 70 region 2, Ankyrin repeats (many copies), CTF / NF I family transcription modulation region, HSF type DNA binding, P53 DNA binding domain, C2H2 type zinc finger (2 copies), Ankyrin repeat, Helix turn helix, OAR domain, Runt domain, pKID domain, P53 tetramerisation motif, Nuclear factor I protein pre N terminus, Sigma 70 region 3, Response regulator receiver domain, Sigma 70 factor, region 1.2, Transcription factor TFIID (or TATA binding protein, TBP), SH2 domain, MarR family, STAT protein, all alpha domain, STAT protein, DNA binding domain, DM DNA binding domain, RFX DNA binding domain, SCAN domain, MH2 domain, Winged helix DNA binding domain, Tesmin / TSOl like CXC domain, Transcriptional regulatory protein, C terminal, Myb / SANT like DNA binding domain, Dof domain, zinc finger, MerR family regulatory protein, MerR HTH family regulatory protein, MarR family, SAND domain, Transcription factor TFIIB repeat, TCP family transcription factor, Domain of unknown function (DUF3371), PHD finger, Sigma 70, non essential region, Hairy Orange, STAT protein, protein interaction domain, Myogenic Basic domain, Auxin response factor, Bacterial regulatory proteins, gntR family, Bacterial regulatory proteins, luxR family, ARID / BRIGHT DNA binding domain, Transcription factor AP 2, Bacterial regulatory proteins, lacl family, Hepatocyte nuclear factor 1 (HNF 1), Nterminus, Holliday junction regulator protein family C terminal repeat, K box region, Myc amino terminal region, PAS domain, Estrogen receptor beta, Zinc finger double stranded RNA binding, Bacterial regulatory helix turn helix proteins, AraC family, Periplasmic binding proteins and sugar binding domain of LacI family, Periplasmic binding protein like domain, Sigma 70, region 4, Glucocorticoid receptor, Alcohol dehydrogenase transcription factor Myb / SANT like, TEA / ATTS domain family, Runx inhibition domain, Homeodomain leucine zipper encoding, Homez, Myc leucine zipper domain, AUX / IAA family, Winged helix turn helix DNA binding, LAG1, DNA binding, Myb / SANT like DNA binding domain, BED zinc finger, Beta trefoil DNA binding domain, TFIIB zinc binding, GATA type transcription activator, N terminal, Periplasmic binding protein domain, CP2 transcription factor, Paired box protein 2 C terminal, Jun like transcription factor, SBP domain, G box binding protein MFMR, Hox protein A13 N terminal, Histone like transcription factor (CBF / NF Y) and archaeal histone, Forkhead N terminal region, C myb, C terminal, SOX transcription factor, Homeobox associated leucine zipper, GCM motif protein, Wilm's tumor protein, Myogenic determination factor 5, lysR family, Core histone H2A / H2B / H3 / H4, Hox9 activation region, MYB CC type transfactor, LHEQLE motif, MerR, DNA binding, Homeodomain like domain, Seed dormancy control, LMSTEN motif, HTH domain, HNF3 C terminal domain, Androgen receptor, Nuclear receptor repeat, helix turn helix, Psq domain, PBC domain, Zinc finger associated domain (zf AD), Engrailed homeobox C terminal signature domain, Hepatocyte nuclear factor 1 (HNF 1), beta isoform C terminus, Transcription factor protein N terminal, Iron dependent repressor, N terminal DNA binding domain, RFX1transcription activation region, Maf N terminal region, SAM domain (Sterile alpha motif), CXXC zinc finger domain, Sox developmental protein N terminal, Domain of unknown function (DUF3446), P53 transactivation motif, Oestrogen receptor, Homeobox protein distal less like N terminal, DeoR like helix turn helix domain, Vertebrate heat shock transcription factor, Sp100 domain, Crp like helix turn helix domain, Sox C terminal transactivation domain, LysR substrate binding domain, Transcriptional regulator, Fungal specific transcription factor domain, IQ calmodulin binding motif, Protein of unknown function DUF260, Zinc finger, C3HC4 type (RING finger), PEA3 subfamily ETS domain transcription factor N terminal domain, Nuclear / hormone receptor activator site AF 1, Zinc finger, C3HC4 type (RING finger), PPAR gamma N terminal region, CCAAT binding transcription factor (CBF B / NF YA) subunit B, Cyclic nucleotide binding domain, T box transcription factor, Bacterial regulatory proteins, crp family, Ring finger domain, START domain, Ferric uptake regulator family, Cro / Cl type HTH DNA binding domain, Iron dependent repressor, metal binding and dimerisation domain, bHLH MYC and R2R3 MYB transcription factors N terminal, Bacterial regulatory protein, Fis family, SET domain, Death domain, Hypoxia inducible factor 1, KilA N domain, ' Cold shock' DNA binding domain, Otxl transcription factor, Caudal like protein activation region, FHA domain, Poly (ADP ribose) polymerase and DNA Ligase Zn finger region, HIF 1 alpha C terminal transactivation domain, Protein of unknown function (DUF3528), Helicase conserved C terminal domain, THAP domain, Sugar specific transcriptional regulator TrmB, Arc like DNA binding domain, Arginine repressor, DNA binding domain, Neuronal helix loop helix transcription factor, Epstein Barr virus nuclear antigen 1, DNA bindingdomain, FeoC like transcriptional regulator, Methyl CpG binding domain, DMRTA motif, Cyclin, N terminal domain, Bacterial regulatory proteins, tetR family, HxlR like helix turn helix, ZF HD protein dimerisation region, BESS motif, Domain of unknown function (DUF4074), Transcriptional regulator PadR like family, linker histone Hl and H5 family, GyrI like small molecule binding domain, Arginine repressor, C terminal domain, MYND finger, Ribbon helix helix protein, copG family, SNF2 family N terminal domain, CCT motif, Basic leucine zipper C terminal, RNA recognition motif, (a. k. a. RRM, RBD, or RNP domain), RNA recognition motif, (a. k. a. RRM, RBD, or RNP domain), Oestrogen type nuclear receptor final C terminal, Ethylene insensitive 3, RNA recognition motif (a. k. a. RRM, RBD, or RNP domain), Helix turn helix domain, Plant zinc cluster domain, Core binding factor beta subunit, Plant protein of unknown function (DUF822), ELK domain, Progesterone receptor, Paired box protein 7, KNOX2 domain, Domain of unknown function (DUF296), Autoinducer binding domain, CG 1 domain, FCD domain, ATPase family associated with various cellular activities (AAA), CoA binding domain, BAH domain, TFIIE alpha subunit, Putative DNA binding protein N terminus, KNOX1 domain, Tc5 transposase DNA binding domain, WRC, TrkA C domain, Hepatocyte nuclear factor 1 (HNF 1), alpha isoform C terminus, HIRAN domain, Zinc knuckle, GA binding protein alpha chain, CarD like / TRCF domain, arsR family, NDT80 / PhoG like DNA binding family, Homeobox prospero like protein (PROX1), Poxvirus D5 protein like, WGR domain, Paired amphipathic helix repeat, F box like, Antitermination protein, PADR1 (NUC008) domain, Ataxin 1 and HBP1 module (AXH), Protein of unknown function, DUF573, hAT family dimerisation domain, pre mRNA splicing factor component, Domain of unknown function (DUF4371),Transcription initiation factor IIF, alpha subunit (TFIIF alpha), NLS binding and DNA binding and dimerisation domains of Nrfl, CodY GAF like domain, Transcriptional activator of glycolytic enzymes, JmjC domain, hydroxylase, BRCA1 C Terminus (BRCT) domain, CASP C terminal, Sigma 54 interaction domain, Poly (ADP ribose) polymerase catalytic domain, DDE superfamily endonuclease, IclR helix turn helix domain, TAZ zinc finger, tify domain, zinc finger of a C2HC type, ECF sigma factor, PRD domain, Domain of unknown function (DUF3432), Penicillinase repressor, Poly (ADP ribose) polymerase, regulatory domain, Trp repressor protein, Herpesvirus ICP4 like protein N terminal region, QLQ, B12 binding domain, FadR C terminal domain, DeoR C terminal sensor domain, Gal4 like dimerisation domain, Brfl like TBP binding domain, E2 (early) protein, C terminal, STE like transcription factor, Tetracycline repressor, C terminal all alpha domain, Nrfl activator activation site binding domain, CodY helix turn helix domain, Bacterial dnaA protein helix turn helix, Copper fist DNA binding domain, Zinc finger, C3HC4 type (RING finger), GAGA binding protein like family, Telomere repeat binding factor (TRF), AAA domain (dynein related subfamily), Transcription factor PAP1, Vertebrate interleukin 3 regulated transcription factor, Aminotransferase class I and II, F box domain, YABBY protein, PAS fold, RNA polymerase Rpbl, domain 5, Divergent CCT motif, Sigma 70 factor, region 1.1, HD ZIP protein N terminus, RNA polymerase Rpbl, domain 4, Bacteriophage CII protein, SKI / SNO / DAC family, CENP B N terminal DNA binding domain, Double sex mab3 related transcription factor 1, UTRA domain, Floricaula / Leafy protein, Zinc knuckle, jmjN domain, RNA polymerase Rpbl, domain 2, RNA polymerase Rpbl, domain 3, Zfx / Zfy transcription activationregion, MEKHLA domain, Transcription initiation factor IIF, beta subunit, Type III restriction enzyme, res subunit, Zinc finger, C2HC type, RNA polymerase Rpbl, domain 1, Bromodomain, BAF1 / ABF1 chromatin reorganising factor, NikR C terminal nickel binding domain, POU domain, class 2, associating factor 1, DDT domain, Histone acetylation protein, Transcription factor IIA, alpha / beta subunit, Fungal protein of unknown function (DUF1752), B box zinc finger, Bacterial transcriptional regulator, MULE transposase domain, Creb binding, Bacterial dna Aprotein, c SKI Smad4 binding domain, ROK family, Metal binding domain of Ada, Transcription initiator DNA binding domain IBD, IstB like ATP binding protein, DEAD / DEAH box helicase, Peptidase S24 like, Sporulation initiation factor SpoOA C terminal, Met Apo repressor, MetJ, RWP RK domain, TRCF domain, Chaperone of endosialidase, Zinc finger, ZZ type, FeoA domain, RNA polymerase Rpbl C terminal repeat, BEN domain, Transcription factor AFT, AsnC family, PAS domain, PurA ssDNA and RNA binding protein, MT A70, Zinc finger protein, KIX domain, Minimal binding motif of Hap4 for binding to Hap2 / 3 / 5, Histidine kinase, DNA gyrase B, and HSP90 like ATPase, AsnC type helix turn helix domain, Domain of unknown function (DUF702), Domain of Unknown Function (DUF902), STAT1 TAZ2 binding domain, Inhibitor of growth proteins N terminal histone binding, C terminal domain of methyl CpG binding protein 2 and 3, RNA polymerase beta subunit, Homeobox protein, Putative binding domain, Cupin like domain, TOBE domain, SWIM zinc finger, Putative helix turn helix protein, YlxM / pl3 like, Cytosine specific DNA methyltransferase replication foci domain, Doublesex dimerisation domain, GAGA factor, RNA polymerase Rpb2, domain 3, Domain of unknown function (DUF313), Churchill protein, FAR1 DNA binding domain,RING H2 zinc finger, Rapl, DNA binding, Putative ATPase subunit of terminase (gpP like), AraC like ligand binding domain, GRF zinc finger, RNA polymerase Rpb2, domain 4, Transferrin, Integrase core domain, SPRY domain, AN1 like Zinc finger, SWIRM domain, RNA polymerase Rpb2, domain 6, RNA polymerase Rpb2, domain 5, WD domain, G beta repeat, Helix turn helix domain of resolvase, Centromere protein B dimerisation domain, Signal transducer and activator of transcription 2 C terminal, GRAS family transcription factor, Oxygenase domain of the 2OGFeDO superfamily, QacR like protein, C terminal region, Histone deacetylase domain, Transcription factor DP, LisH, LexA DNA binding domain, RecF / RecN / SMC N terminal domain, Domain of unknown function DUF120, DnaA N terminal domain, RING type zinc finger, LisH dimerisation motif, Brinker DNA binding domain, Amino acid kinase family, RNA polymerase Rpbl, domain 7, Protein kinase domain, N terminal domain of DPF2 / REQ., Transcription factor Vhrl, Glycosyl hydrolase family 14, Domain of unknown function (DUF2028), mTERF, RNA polymerase Rpb2, domain 7, RNA polymerase Rpbl, domain 6, Protein tyrosine kinase, Associated with HOX, AAA domain (Cdc48 subfamily), Fushi tarazu (FTZ), N terminal region, RING variant domain, PB1 domain, CBS domain, RNA polymerase Rpb2, domain 2, Lectin C type domain, Ubiquitin C terminal hydrolase 37 receptor binding site, CAT RNA binding domain, Phosphoribosyl transferase domain, Phi 29 like late genes activator (early protein GP4), Protein of unknown functionDUF134, C 5 cytosine specific DNA methylase, Arginase family, Alpha / beta hydrolase family, Nucleopolyhedrovirus late expression factor 3 (LEF 3), H NS histone family, TFIIE beta subunit core domain, PBP superfamily domain, PLATZ transcription factor, Complexl_LYR like, Histidine kinase, DNA gyrase B, and HSP90 like ATPase, BSD domain,Sec7 domain, Sigma 54 modulation protein / S30EA ribosomal protein, TipAS antibiotic recognition domain, Thiolase, C terminal domain, PCI domain, Zn finger in Ran binding protein and others, DMAP1 binding Domain, Mannitol dehydrogenase Rossmann domain, GAF domain, DNA binding protein S1FA, Protein of unknown function (DUF3591), CW type Zinc Finger, ARC105 or Medl5 subunit of Mediator complex non fungal, Oxidoreductase family, NAD binding Rossmann fold, Semialdehyde dehydrogenase, NAD binding domain, Guanine nucleotide exchange factor in Golgi transport N terminal, Cytochrome C and Quinol oxidase polypeptide I, E2 (early) protein, N terminal, NOPS (NUC059) domain, phosphotransferase system, EIIB, YL1 nuclear protein, KorB domain, 6 0 methylguanine DNA methyltransferase, DNA binding domain, Mannitol dehydrogenase C terminal domain, Poxvirus early transcription factor (VETF), large subunit, GAF domain, Herpesvirus transcription activation factor (transactivator), Leucine Rich repeat, Transcription factor Opil, ATP cone domain, P protein C terminus, DHHC palmitoyltransferase, YsiA like protein, C terminal region, XPA protein N terminal, CoA binding domain, dimerisation domain, Acetyltransferase (GNAT) family, TLC domain, Phosphotransferase system, EIIC, YL1 nuclear protein C terminal domain, Ribosomal protein L16p / L10e, Domain of unknown function (DUF4195), G patch domain, Plus 3 domain, Bacterial purine repressor, N terminal, Rapl C terminal domain, Zinc binding, KH domain, HAMP domain, GAF domain, Tryptophan RNA binding attenuator protein, F / Y rich N terminus, Transcriptional activator TraM, XPA protein C terminus, Exonuclease, Protein of unknown function (DUF619), Pyridine nucleotide disulfide oxidoreductase, His (2) Cys (2) zinc finger, Zinc carboxypeptidase, Bacterial transferase hexapeptide (sixrepeats), DExH box splicing factor binding site, 6 0 methylguanine DNA methyltransferase, ribonuclease like domain, Bacterial DNA binding protein, OTU like cysteine protease, Mating type protein MAT alpha 1, B block binding subunit of TFIIIC, MamL 1 domain, KH domain, Firmicute transcriptional repressor of class III stress genes (CtsR), Histidine kinase, Zinc finger of the MIZ type in Nse subunit, Metallo beta lactamase superfamily, Basic membrane protein, F / Y rich C terminus, Eukaryotic translation initiation factor eIF2A, UBA / TS N domain, BTB And C terminal Kelch, SAM domain (Sterile alpha motif), Aftl osmotic stress response (OSM) domain, Pyridine nucleotide disulfide oxidoreductase, Interferon induced 35 kDa protein (IFP 35) N terminus, Protein of unknown function (DUF2817), Sin3 binding region of histone deacetylase complex subunit SAP30, HrcA protein C terminal domain, Magnesium chelatase, subunit Chll, Archaeal ATPase, Transcriptional regulator DELLA protein N terminal, Maltose acetyltransferase, Suppressor of cytokine signalling, SI RNA binding domain, 3H domain, ABA / WDS induced protein, Transcription factor CRF1, Domain of unknown function (DUF3518), Recombinase Flp protein N terminus, Beta lactamase superfamily domain, PHD like zinc binding domain, Myelin gene regulatory factorC terminal domain 1, Aldehyde dehydrogenase family, Nuclear pore complex assembly, Putative GTPase activating protein for Arf, Anti repressor SinI, Antidote toxin recognition MazE, SSXRD motif, CBF / Mak21 family, L lysine 6 monooxygenase (NADPH requiring), Adenylate and Guanylate cyclase catalytic domain, Flagellar transcriptional activator (FlhD), PTS system fructose IIA component, AAA domain, Stage III sporulation protein D, Transcription factor / nuclear export subunit protein 2, NusA N terminal domain, Reverse transcriptase like, SMCproteins Flexible Hinge Domain, short chain dehydrogenase, Glycerol 3 phosphate responsive antiterminator, alpha / beta hydrolase fold, Recombinase Flp protein, Domain of unknown function (DUF3425), His Kinase A (phospho acceptor) domain, Family description, PHD zinc finger like domain, PTS HPr component phosphorylation site, DDE superfamily endonuclease, Transcriptional enhancer, Asx hm domain, DnaJ domain, SPFH domain / Band 7 family, Myelin gene regulatory factor C terminal domain 2, Proline dehydrogenase, Cro, Domain of unknown function (DUF4171), CHY zinc finger, Pyridine nucleotide disulfide oxidoreductase, Protein phosphatase 2C, YcdC like protein, C terminal region, Ribosomal protein L35Ae, C5HC2 zinc finger, Transcription and export related complex subunit, Uncharacterized protein family (UPF0121), NusA like KH domain, PAS domain, AAA domain, Domain of unknown function (DUF3594), Alpha / beta hydrolase family, Peptidase family Ml, GDSL like Lipase / Acylhydrolase, Complex 1 protein (LYR family), Winged helix turn helix, Ubiquitin associated domain (UBA), Winged helix turn helix transcription repressor, HrcA DNA binding, Transcriptional regulator, Serpentine type 7TM GPCR chemoreceptor Srh, Putative Sin3 binding protein, Thiolase, N terminal domain, CpG binding protein zinc finger C terminal domain, PucR C terminal helix turn helix domain, PLU 1 like protein, EVE domain, SPT2 chromatin protein.

66. A full hybrid peptide in Claim 1 comprised of one or multiple DNA binding stretches and one or multiple NLS sequences with or without spacers.

67. A full hybrid peptide in Claim 1 comprised of at least 4 consecutive amino acids of the NLS sequence KQRDAEHRDRTKKKKRSRSRDRNRDRDRDRERNRDRDHKRRHRSRSRSRSRTRERNK VKSRYRSRSRSQSPPKDRKDRDK and at least 4 consecutive aminoacids of the DNA binding stretch CSTLNFTLDLSRNNLVTVQPEMFAQLSHLQCLRLSHNCISQAVNGSQFLPLTGLQVL DLSHNKLDLYHEHSFTELPRLEALDLSYNSQPFGMQGVGHNFSFVAHLRTLRHLSLA HNNIHSQVSQQLCSTSLRALDFSGNALGHMWAEGDLYLH.

68. A full hybrid peptide in Claim 1 comprised of at least 4 consecutive amino acids of the NLS sequence MMPNKVRKIGELVRYLNTNPVGGLLEYARSHGFAAEFKLVDQSGPPHEPKFVYQAKV GGRWFPAVCAHSKKQGKQEAADAALRVLIGENEKAER, at least 4 consecutive amino acids of the DNA binding stretch SGYHYGVSSCEGCKGFFRRSIQKNMVYTCHRDKNCI INKVTRNRCQYCRLQKCFEVG MSKEAVRNDRNKKKKEVKEEGSPDSYE, and at least 4 consecutive amino acids of the NLS sequence GRNRAPELGAPGIQKKKR.

69. A full hybrid peptide in Claim 1 comprised of at least 4 consecutive amino acids of the NLS sequence PRRTTRRHPNTQQRASKKKPK, at least 4 consecutive amino acids of the spacer sequence AKKSKTAAKKNDKEAAG, and at least 4 consecutive amino acids of the DNA binding stretchRL AANARE RRRMHGLNHAFD Q LRNV IPSFNNDKKLSK.

70. A full hybrid peptide in Claim 1 comprised of at least 4 consecutive amino acids of the NLS sequence KRPAATKKAGQAKKK, at least 4 consecutive amino acids of the spacer sequence DEKTEESDTDRLLSSDHEKSHSNLGV, at least 4 consecutive amino acids of the DNA binding stretch RAHHNALERKRRDHIKDSFHSLRDSVPSLQGEKASR, at least 4 consecutive amino acids of the spacer sequence GGGGSGGGGSGGGGSGGGGS, and at least 4 consecutive amino acids of the NLS sequence KRMNAFMVWAQAARRK.

71. A full hybrid peptide in Claim 1 comprised of up to 3 NLSs optionally interspersed with spacers and up to 3 DNA binding stretches optionally interspersed with spacers, such that the NLSs are comprised of at least 4 consecutive amino acids from each of the following sequences RQARRNRRRRWR, CYGSKNTGAKKRKIDDA, RKHKTNRKPR, spacers which may be comprised of at least 4 consecutiveamino acids from each of the following sequences GSAGSAAGSGEF, SDQEAKPSTEDLG, RWPESPKAQASSVPTAQPQAEGSLAKATTAPATTRNT, and DNA binding sites that are comprised of at least 4 consecutive amino acids from each of the following sequencesRKLKNRVAAQT ARD RK, KRKRRGNLPKESVKILRDWLYLHRYNAYPSEQEKLSLSGQTNLSVLQICNWFINARRR, AWQNSIRHNLSLNDCFVKIPREPGNPGKGNYWTLDPQSEDMFDNGSFLRRRKR.

72. A full hybrid peptide in Claim 1 comprised of up to 3 NLSs optionally interspersed with spacers and up to 3 DNA binding stretches optionally interspersed with spacers, such that the NLSs are comprised of at least 4 consecutive amino acids from each of the following sequences SQKHLQINQTFEELRLVT,RKP VT AQE RQRE RE E KRRRRQE RAKE RE KRRQE RE R, KRPMNAF I VWS RD QRRK, spacers which may be comprised of at least 4 consecutive amino acids from each of the following sequences APELLGGP, PVPSTPPTPSPSTPPTPSPSC, AKAEAGAEAGGGAGPGAEDEAGRGAVGDPELGDPPAAPQ, and DNA binding sites that are comprised of at least 4 consecutive amino acids from each of the following sequences PLWRRDGTGHYLCNACGLYHKMNGQNRPLIKPTSCANCQTTTTTLWRRNANGDPVCN ACGLYYKLHNINRPLTMKKEGIQTRNRKM, LTTEADSGY, KTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNN CCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELV FQVKTLSLPVWIVHGSQ.

73. A full hybrid peptide in Claim 1 comprised of an NLS sequence and a DNA binding stretch from a protein moderately to highly expressed in adipocytes, which contains EYQSAIKVEPASPPYYSEKTQLYNRPHEEPSNSLMAISGFHYGVHACEGCKGFFRRT IRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEK.

74. A full hybrid peptide in Claim 1 comprised of an NLS, a DNA binding stretch from a protein moderately tohighly expressed in adipocytes, and an NLS, which contains PAAKRVKLDRENHSEIERRRRNKMTAYITELSDMVPTCPDKPAAKRVKLD.

75. A full hybrid peptide in Claim 1 comprised of an NLS, a spacer sequence, and a DNA binding stretch from a protein moderately to highly expressed in adipocytes, which containsRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEK LLAEGGGGSGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKN ENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTV LFESQFSVGSNELVFQVKTLSLPVWIVHGSQ.

76. A full hybrid peptide in Claim 1 comprised of an NLS, a spacer, a DNA binding stretch from a protein moderately to highly expressed in adipocytes, a spacer, and an NLS, which contains SQKHLQINQTFEELRLVTGGGGSRERNNIAVRKSRGGGGSSQKHLQINQTFEELRLVT.

77. A full hybrid peptide in Claim 1 comprised of 3 NLSs interspersed with spacers, a DNA binding stretch from a protein moderately to highly expressed in adipocytes, and 3 NLSs interspersed with spacers, which contains RRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEK LLAEGSAGSAAGSGEFPAAKRVKLDGSAGSAAGSGEFSQKHLQINQRFEELRLITKR RHRTTFTSLQLEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRKS QKHLQINQRFEELRLITGSAGSAAGSGEFPAAKRVKLDGSAGSAAGSGEFRRTIRLK LI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKLLAE.

78. A full hybrid peptide in Claim 1 comprised of 3 NLSs, 3 DNA binding stretches from one or more proteins moderately to highly expressed in adipocytes, and 3 NLSs, all interspersed with spacers, which contains SQKHLQINQTFEELRLVTGGGGSGGGGSGGGGSEYQSAIKVEPASPP YYSEKTQLYN RPHEEPSNSLMAIGGGGSGGGGSGGGGSPAAKRVKLDGGGGSGGGGSGGGGSSGFHY GVHACEGCKGFFRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAI RFGRMPQAEKEKGGGGSGGGGSGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADR RGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPVWIVHGSQGGGGSGGGGSGG GGSRERNNIAVRKSRGGGGSGGGGSGGGGSPAAKRVKLDGGGGSGGGGSGGGGSEYQ SAIKVEPASPP YYSEKTQLYNRPHEEPSNSLMAIGGGGSGGGGSGGGGSSQKHLQIN QTFEELRLVT.

79. A full hybrid peptide in Claim 1 comprised of up to 3 repeats of an NLS-DNA binding stretch unit derived from proteins moderately to highly expressed in adipocytes and connected by flexible spacers, with an amino acid sequence that contains CYGSKNTGAKKRKIDDAKSNPSKRHRDGGGGSGGGGSGGGGSGGGGSCYGSKNTGAK KRKIDDAKSNPSKRHRDGGGGSGGGGSGGGGSGGGGSCYGSKNTGAKKRKIDDAKSN PSKRHRD.

80. A full hybrid peptide in Claim 1 comprised of up to 3 different NLS-DNA binding stretch units derived from proteins moderately to highly expressed in adipocytes and connected by flexible spacers, with an amino acid sequence that contains KRMNAFMVWAQAARRKSGFHYGVHACEGCKGFFRRTIRLKLI YDRCDLNCRIHKKSR NKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKEKGGGGSGGGGSGGGGSKRPAATKKA GQAKKKNHNILERQRRNDLRSSFLTLRDHVPELVKNEKAAKGGGGSGGGGSGGGGSC YGSKNTGAKKRKIDDAKSNPSKRHRD.

81. A full hybrid peptide in Claim 1 comprised of one or multiple DNA binding stretches and one or multiple NLS sequences interspersed with spacers, which is PAAKRVKLDGGGGSPAAKRVKLDGGGGSPAAKRVKLDGGGGSKSNPSKRHRDGGGGS GGGGSKSNPSKRHRDGGGGSGGGGSKSNPSKRHRDGGGGSPAAKRVKLDGGGGSPAA KRVKLDGGGGSPAAKRVKLD.

82. A full hybrid peptide in Claim 1 comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is KRMNAFMVWAQAARRKAPELLGGPCKRKTTNADRRKAAPELLGGPGRNRAPELGAPG IQKKKRAPELLGGPRLMKNREAARECRGGGGSRRSKNRIAAQRCRKRKGGGGSRREKNKVAAARCRNKKAPELLGGPGRNRAPELGAPGIQKKKRAPELLGGPCKRKTTNADRR KAAPELLGGPKRMNAFMVWAQAARRK.

83. A full hybrid peptide in Claim 1 comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is SQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVTGGGGSSQKHLQINQTF EELRLVTGGGGSKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLKNEN TRNECSGEILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFTVLF ESQFSVGSNELVFQVKTLSLPVWIVHGSQGSAGSAAGSGEFKTQTKFAATVRLLVG GKLNVHMNPPQVKATIISEQQAKSLLKNENTRNECSGEILNNCCVMEYHQATGTLSA HFRNMSLKRIKRADRRGAESVTEEKFTVLFESQFSVGSNELVFQVKTLSLPVWIVH GSQGSAGSAAGSGEFKTQTKFAATVRLLVGGKLNVHMNPPQVKATIISEQQAKSLLK NENTRNECSGEILNNCCVMEYHQATGTLSAHFRNMSLKRIKRADRRGAESVTEEKFT VLFESQFSVGSNELVFQVKTLSLPVWIVHGSQGGGGSSQKHLQINQTFEELRLVTG GGGSSQKHLQINQTFEELRLVTGGGGSSQKHLQINQTFEELRLVT.

84. A full hybrid peptide in Claim 1 comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is GKKKKGKPGKRREQRKKKRRTGGGGSGGGGSGGGGSGGGGSSGFHYGVHACEGCKGF FRRTIRLKLI YDRCDLNCRIHKKSRNKCQYCRFQKCLAVGMSHNAIRFGRMPQAEKE KGGGGSGGGGSGGGGSGGGGSRREKNKVAAARCRNKKGGGGSGGGGSGGGGSGGGGS KRRHRTTFTSLQLEELEKVFQKTHYPDVYVREQLALRTELTEARVQVWFQNRRAKWRK.

85. A full hybrid peptide in Claim 1 comprised of one or multiple DNA binding stretches and NLS sequences interspersed with spacers, which is CYGSKNTGAKKRKIDDAGGGGSGGGGSGGGGSRRERNKIAAAKCRNKKRWPESPKAQ ASSVPTAQPQAEGSLAKATTAPATTRNTNKQGWQNSIRHNLSLNECFVKVPRDDKKP GKGSYWTLDPDSYNMFENGSFLRRRRRGGGGSGGGGSGGGGSKRKKEMANKSAPEAK KKK.

86. A critical pairing number in Claim 1, which is 1.

87. A critical pairing number in Claim 1, which is greater than 1 but smaller than 8.

88. A critical pairing number in claim 1, which is greater than 1 but smaller than 37.

89. A peptide in Claim 1 with CG binding stretches derived at least in part from a Toll-like receptor and combined with at least one amino acid stretch which serves as a nuclear localization sequence.

90. A peptide in Claim 1 with at least one DNA binding stretch derived at least in part from a Zinc Finger protein, Homeobox domain, Leucine Rich Domain, Leucine Rich Repeat, basic Helix-Loop-Helix motif, Chromo domain, Chromo-like domain superfamily domain, basic Leucine Zipper domain, or a domain comprised of at least one LXXXXXL motif where L is either a Leucine or Isoleucine, and combined with at least one amino acid stretch which serves as a nuclear localization sequence.

91. Non-viral gene delivery vehicles in Claim 1, which are lipid nanoparticles.

92. Non-viral gene delivery vehicles in Claim 1, which are virus-like particles.

93. Non-viral gene delivery vehicles in Claim 1, which are peptide or polymer carriers.

94. Non-viral gene delivery vehicles in Claim 1, which are lipid nanoparticles with covalently attached targeting moieties.

95. Non-viral gene delivery vehicles in Claim 1, which are lipid nanoparticles with one or more targeting moieties on the surface.

96. Non-viral gene delivery vehicles in Claim 1, which are polymeric nanoparticles.

97. Non-viral gene delivery vehicles in Claim 1, which are nanoparticles comprised of lipid and non-lipid components.

98. Non-viral gene delivery vehicles in Claim 1, which are polymeric nanoparticles comprised of polymer and nonpolymer components.

99. Non-viral gene delivery vehicles in Claim 1, which are comprised at least in part of metallic nanoparticles.

100. Non-viral gene delivery vehicles in Claim 1, which are physical methods of gene delivery.

101. DNA sequences in Claim 1, which contain HRACCACGTGGTYD.

102. DNA sequences in Claim 1, which contain TASCACRTGTCW.

103. DNA sequences in Claim 1, which contain GCCAYGYGSS.

104. DNA sequences in Claim 1, which contain MRMGTRHCACGTGD YACKYK.

105. DNA sequences in Claim 1, which contain CACGTGS.

106. DNA sequences in Claim 1, which contain CCACSTGWCY.

107. DNA sequences in Claim 1, which contain RACCACGTGSTC.

108. DNA sequences in Claim 1, which contain KACCACGTGSYY.

109. DNA sequences in Claim 1, which contain CASGTGGC.

110. DNA sequences in Claim 1, which contain RGCCACGTGCC.

111. DNA sequences in Claim 1, which contain GASCACGTGGY.

112. DNA sequences in Claim 1, which contain RASCACGTGGT.

113. DNA sequences in Claim 1, which contain SSCCACGTGCYS.

114. DNA sequences in Claim 1, which contain CCACGTGC.

115. DNA sequences in Claim 1, which contain CCACGTGAA.

116. DNA sequences in Claim 1, which contain CGTGG.

117. DNA sequences in Claim 1, which contain CACGTGC.

118. DNA sequences in Claim 1, which contain CGTGC.

119. DNA sequences in Claim 1, which contain GCACGTGCT.

120. DNA sequences in Claim 1, which containYMCCACGTGYMV.

121. DNA sequences in Claim 1, which contain SSSCACGYGS.

122. DNA sequences in Claim 1, which contain CCACGTGS.

123. DNA sequences in Claim 1, which contain SGCCACGTGGCS.

124. DNA sequences in Claim 1, which contain CCACGTGG.

125. DNA sequences in Claim 1, which contain GGCACGTGKY.

126. DNA sequences in Claim 1, which contain SCACGTGS.

127. DNA sequences in Claim 1, which contain RRMCACGTGR.

128. DNA sequences in Claim 1, which contain CCACGTG.

129. DNA sequences in Claim 1, which contain SVRTGASTCAKCM.

130. DNA sequences in Claim 1, which contain TGACTCAWKSKB.

131. DNA sequences in Claim 1, which contain RTGACTCAD 132. DNA sequences in Claim 1, which contain TGAGTCAK.

133. DNA sequences in Claim 1, which contain TGACTCAB.

134. DNA sequences in Claim 1, which contain GRTGACGTCAYC.

135. DNA sequences in Claim 1, which contain GRTGAWTCAYC.

136. DNA sequences in Claim 1, which contain AATGAYRCG.

137. DNA sequences in Claim 1, which contain RATGAYRCG.

138. DNA sequences in Claim 1, which contain KATGASTCAYM.

139. DNA sequences in Claim 1, which contain DRTGACTCATY.

140. DNA sequences in Claim 1, which contain RRTGASTCAKS.

141. DNA sequences in Claim 1, which contain KKRTGACTCATMM.

142. DNA sequences in Claim 1, which contain DRATGACTCATHY.

143. DNA sequences in Claim 1, which contain ATGACTCAT.

144. DNA sequences in Claim 1, which contain RTGACTCAT.

145. DNA sequences in Claim 1, which contain YKRTGACTMATMC.

146. DNA sequences in Claim 1, which contain RRTGACTMAT.

147. DNA sequences in Claim 1, which contain RTGACGYMAY.

148. DNA sequences in Claim 1, which contain TGASTCAYCH.

149. DNA sequences in Claim 1, which contain RTGACTCAYYC 150. DNA sequences in Claim 1, which contain KRRTGASTCAB 151. DNA sequences in Claim 1, which contain GRTGACGTMAT 152. DNA sequences in Claim 1, which contain RRTGASTCAB.

153. DNA sequences in Claim 1, which contain RTGAGTCAY.

154. DNA sequences in Claim 1, which contain RTGACGTMAT.

155. DNA sequences in Claim 1, which contain RTGASTCA.

156. DNA sequences in Claim 1, which contain KRTGASTCAY.

157. DNA sequences in Claim 1, which contain KRTGACGTCAYM.

158. DNA sequences in Claim 1, which contain KKRTKACGTCAYCGC.

159. DNA sequences in Claim 1, which contain KKRTGAGTCAYM.

160. DNA sequences in Claim 1, which contain KRTGASTCAYMV.

161. DNA sequences in Claim 1, which contain KKRTGAGTCAYMV.

162. DNA sequences in Claim 1, which contain RTGAGTCAYM.

163. DNA sequences in Claim 1, which contain DRTGACGTCATMMKTY.

164. DNA sequences in Claim 1, which contain TGAMTCA.

165. DNA sequences in Claim 1, which contain TGACTCAK.

166. DNA sequences in Claim 1, which contain KKWATGASKCATMY.

167. DNA sequences in Claim 1, which contain RTGAGTCAYCS.

168. DNA sequences in Claim 1, which contain DVTGASTCATB.

169. DNA sequences in Claim 1, which contain BGATGACGTCATCR.

170. DNA sequences in Claim 1, which contain TGASTCAT.

171. DNA sequences in Claim 1, which containGATGACGTCATCR.

172. DNA sequences in Claim 1, which contain GATGACGTCAYC.

173. DNA sequences in Claim 1, which contain GATGAYGTCATC.

174. DNA sequences in Claim 1, which contain AGTCA.

175. DNA sequences in Claim 1, which contain TGACTCA.

176. DNA sequences in Claim 1, which contain RSTGACTCMGW.

177. DNA sequences in Claim 1, which contain ACSMGGAAGTR.

178. DNA sequences in Claim 1, which contain RASRMGGAAGTR.

179. DNA sequences in Claim 1, which contain GAMCCGGAAGTR.

180. DNA sequences in Claim 1, which contain AACRAGGAAGTR.

181. DNA sequences in Claim 1, which contain AASRAGGAAGTR.

182. DNA sequences in Claim 1, which contain WAYWTCCKK.

183. DNA sequences in Claim 1, which contain YYWRRGGTCAAAGGTCAHVBD.

184. DNA sequences in Claim 1, which contain AASTRGGTCACSGTGACCYACWT.

185. DNA sequences in Claim 1, which containWAS YRGGKCAAAGKTCA.

186. DNA sequences in Claim 1, which contain WGAMCTTTGACCY.

187. DNA sequences in Claim 1, which contain AGGTCAG 188. DNA sequences in Claim 1, which contain AWSTRGGKCAAAGGKCA.

189. DNA sequences in Claim 1, which contain YYWRRGGTCAAAGGTCAYMK.

190. DNA sequences in Claim 1, which contain STRGGTCACSGTGACCYACW.

191. DNA sequences in Claim 1, which contain TRGGTCACSGTGACCYACW.

192. DNA sequences in Claim 1, which contain AWSTRGGTYAST.

193. DNA sequences in Claim 1, which contain MRRGGKYAAWRGGTCAC.

194. DNA sequences in Claim 1, which contain AANNNAGGTCANNGGNCA.

195. DNA sequences in Claim 1, which contain AANNAGGTNANNGGTCA.

196. DNA sequences in Claim 1, which contain AAANNAGGTCA.

197. DNA sequences in Claim 1, which contain TGNCNNNTGACCTNNNTT.

198. DNA sequences in Claim 1, which contain TGACCTNNNTT.

199. DNA sequences in Claim 1, which contain ARRGGTCAAAGGTCAH.

200. DNA sequences in Claim 1, which contain RRGGTCAAAGGTCA.

201. DNA sequences in Claim 1, which containCWRAWC YAGGYCAWAGKTCA.

202. DNA sequences in Claim 1, which contain YMRGGTCATWGGGGTSARG.

203. DNA sequences in Claim 1, which contain TGACCTY.

204. DNA sequences in Claim 1, which contain RGGTCARAGGTCA.

205. DNA sequences in Claim 1, which contain AWGTRGGTCAAAGGTCAT.

206. DNA sequences in Claim 1, which contain AWGTRGGTCAAAGGTCA.

207. DNA sequences in Claim 1, which contain ARRGGTCRTGACCYYT.

208. DNA sequences in Claim 1, which contain DGRGGTCAAAGGTCRY.

209. DNA sequences in Claim 1, which contain ARRGGTCGYGACCYYK.

210. DNA sequences in Claim 1, which contain MSTGWCCTB.

211. DNA sequences in Claim 1, which contain RGGTCAR.

212. DNA sequences in Claim 1, which contain AAAAGGTCAM.

213. DNA sequences in Claim 1, which containRAGGTC AAAAGGTCAM.

214. DNA sequences in Claim 1, which contain RAGGTCRTGACCTY.

215. DNA sequences in Claim 1, which contain AAAAGGTCAH.

216. DNA sequences in Claim 1, which contain RAGGTCAAAAGGTCAH.

217. DNA sequences in Claim 1, which contain RAGGTCRTGACCT.

218. DNA sequences in Claim 1, which contain CCAGGTGG.

219. DNA sequences in Claim 1, which contain GCCACCTGSCTGYD.

220. DNA sequences in Claim 1, which contain CCACCTGCMN.

221. DNA sequences in Claim 1, which contain DRCAGGTGYR.

222. DNA sequences in Claim 1, which contain RCAGGTG.

223. DNA sequences in Claim 1, which contain ARCAGGTGCA.

224. DNA sequences in Claim 1, which contain RRCAGGTGYR.

225. DNA sequences in Claim 1, which contain RRCAGGTGCR.

226. DNA sequences in Claim 1, which contain YCAGGTG.

227. DNA sequences in Claim 1, which contain KCACCTGM.

228. DNA sequences in Claim 1, which contain SSSRSCKCACCTGS.

229. DNA sequences in Claim 1, which contain CACCTGSRK.

230. DNA sequences in Claim 1, which contain RRCAGGTGY.

231. DNA sequences in Claim 1, which contain AYGCACCTGTMRY.

232. DNA sequences in Claim 1, which contain GCACCTGT.

233. DNA sequences in Claim 1, which contain WWWMRAKRCACCTGYTAKWHAW.

234. DNA sequences in Claim 1, which contain TTCCCRKAA.

235. DNA sequences in Claim 1, which contain DAWTTCYWGGAAWYH.

236. DNA sequences in Claim 1 which contain TTCCCRGAAWTBSKWTWCCKRGRR.

237. DNA sequencesClaim 1 which contain YAWTTCYW.

238. DNA sequencesClaim 1 which contain SWYTTCYW.

239. DNA sequencesClaim 1 which contain KRYWYTTCYKRGA.

240. DNA sequencesClaim 1 which contain RSWTTTCTARGAA.

241. DNA sequencesClaim 1 which contain TTCYYRGAAAY.

242. DNA sequencesClaim 1 which contain TTTCYKRGAAW.

243. DNA sequencesClaim 1 which contain KAWTTCYTGGAAWTY.

244. DNA sequencesClaim 1 which contain RAWTTCCARGAAWTM.

245. DNA sequencesClaim 1 which contain TTTCYKRGAAA.

246. DNA sequencesClaim 1 which contain TTCYYAGGAAWYT.

247. DNA sequencesClaim 1 which contain TTCCNGGAA.

248. DNA sequencesClaim 1 which contain TTCCTGGAA.

249. DNA sequencesClaim 1 which contain CCNNGGAANNNNNA.

250. DNA sequencesClaim 1 which contain TTCC.

251. DNA sequencesClaim 1 which contain GGAANNNNNA.

252. DNA sequencesClaim 1 which contain TTCNNGG.

253. DNA sequencesClaim 1 which contain at least two of the following sequences HRACCACGTGGTYD, TASCACRTGTCW GCCAYGYGSS, MRMGTRHCACGTGDYACKYK, CACGTGS, CCACSTGWCY RACCACGTGSTC, KACCACGTGSYY, CASGTGGC, RGCCACGTGCC, GASCACGTGGY, RASCACGTGGT, SSCCACGTGCYS, CCACGTGC, CCACGTGAA, CGTGG, CACGTGC, CGTGC, GCACGTGCT, YMCCACGTGYMV, SSSCACGYGS, CCACGTGS, SGCCACGTGGCS, CCACGTGG, GGCACGTGKY, SCACGTGS, RRMCACGTGR, CCACGTG, SVRTGASTCAKCM, GACTCAWKSKB, TGACTCAD, TGAGTCAK, TGACTCAB, GRTGACGTCAYC, GRTGAWTCAYC, ATGAYRCG, ATGAYRCG,KATGASTCAYM, DRTGACTCATY, RRTGASTCAKS, KKRTGACTCATMM, DRATGACTCATHY, ATGACTCAT, RTGACTCAT, YKRTGACTMATMC, RRTGACTMAT, RTGACGYMAY, TGASTCAYCH, RTGACTCAYYC, KRRTGASTCAB, GRTGACGTMAT, RRTGASTCAB, RTGAGTCAY, RTGACGTMAT, RTGASTCA, KRTGASTCAY, KRTGACGTCAYM, KKRTKACGTCAYCGC, KKRTGAGTCAYM, KRTGASTCAYMV, KKRTGAGTCAYMV, RTGAGTCAYM, DRTGACGTCATMMKTY, TGAMTCA, TGACTCAK, KKWATGASKCATMY, RTGAGTCAYCS, DVTGASTCATB, BGATGACGTCATCR, TGASTCAT, ATGACGTCATCR, ATGACGTCAYC, GATGAYGTCATC, AGTCA, TGACTCA, RSTGACTCMGW, ACSMGGAAGTR, RASRMGGAAGTR, GAMCCGGAAGTR, AACRAGGAAGTR, ASRAGGAAGTR, AYWTCCKK, YYWRRGGTCAAAGGTCAHVBD, AASTRGGTCACSGTGACCYACWT, WASYRGGKCAAAGKTCA, WGAMCTTTGACCY, AGGTCAG, AWSTRGGKCAAAGGKCA, YYWRRGGTCAAAGGTCAYMK, STRGGTCACSGTGACCYACW, TRGGTCACSGTGACCYACW, AWSTRGGTYAST, MRRGGKYAAWRGGTCAC, AANNNAGGTCANNGGNCA, AANNAGGTNANNGGTCA, AAANNAGGTCA, TGNCNNNTGACCTNNNTT, TGACCTNNNTT, ARRGGTCAAAGGTCAH, RRGGTCAAAGGTCA, CWRAWCYAGGYCAWAGKTCA, YMRGGTCATWGGGGTSARG, TGACCTY, RGGTCARAGGTCA, AWGTRGGTCAAAGGTCAT, AWGTRGGTCAAAGGTCA, ARRGGTCRTGACCYYT, DGRGGTCAAAGGTCRY, ARRGGTCGYGACCYYK, MSTGWCCTB, RGGTCAR, AAAAGGTCAM, RAGGTCAAAAGGTCAM, RAGGTCRTGACCTY, AAAAGGTCAH, RAGGTCAAAAGGTCAH, RAGGTCRTGACCT, CCAGGTGG, GCCACCTGSCTGYD, CCACCTGCMN, DRCAGGTGYR, RCAGGTG, ARCAGGTGCA, RRCAGGTGYR, RRCAGGTGCR, YCAGGTG, KCACCTGM, SSSRSCKCACCTGS, CACCTGSRK, RRCAGGTGY, AYGCACCTGTMRY, GCACCTGT, WWWMRAKRCACCTGYTAKWHAW, TTCCCRKAA, DAWTTCYWGGAAWYH, TTCCCRGAAWTBSKWTWCCKRGRR, YAWTTCYW, SWYTTCYW, KRYWYTTCYKRGA, RSWTTTCTARGAA, TTCYYRGAAAY, TTTCYKRGAAW, KAWTTCYTGGAAWTY, RAWTTCCARGAAWTM, TTTCYKRGAAA, TTCYYAGGAAWYT, TTCCNGGAA, TTCCTGGAA, CCNNGGAANNNNNA, TTCC, GGAANNNNNA, TTCNNGG.

254. DNA sequences in Claim 1, which contain at least 80% of at least one of the following sequencesHRACCACGTGGTYD, TASCACRTGTCW, GCCAYGYGSS, MRMGTRHCACGTGDYACKYK, CACGTGS, CCACSTGWCY, RACCACGTGSTC, KACCACGTGSYY, CASGTGGC, RGCCACGTGCC, GASCACGTGGY, RASCACGTGGT, SSCCACGTGCYS, CCACGTGC, CCACGTGAA, CGTGG, CACGTGC, CGTGC, GCACGTGCT, YMCCACGTGYMV, SSSCACGYGS, CCACGTGS, SGCCACGTGGCS, CCACGTGG, GGCACGTGKY, SCACGTGS, RRMCACGTGR, CCACGTG, SVRTGASTCAKCM, GACTCAWKSKB, TGACTCAD, TGAGTCAK, TGACTCAB, GRTGACGTCAYC, GRTGAWTCAYC, ATGAYRCG, ATGAYRCG, KATGASTCAYM, DRTGACTCATY, RRTGASTCAKS, KKRTGACTCATMM, DRATGACTCATHY, ATGACTCAT, RTGACTCAT, YKRTGACTMATMC, RRTGACTMAT, RTGACGYMAY, TGASTCAYCH, RTGACTCAYYC, KRRTGASTCAB, GRTGACGTMAT, RRTGASTCAB, RTGAGTCAY, RTGACGTMAT, RTGASTCA, KRTGASTCAY, KRTGACGTCAYM, KKRTKACGTCAYCGC, KKRTGAGTCAYM, KRTGASTCAYMV, KKRTGAGTCAYMV, RTGAGTCAYM, DRTGACGTCATMMKTY, TGAMTCA, TGACTCAK, KKWATGASKCATMY, RTGAGTCAYCS, DVTGASTCATB, BGATGACGTCATCR, TGASTCAT, ATGACGTCATCR, ATGACGTCAYC, GATGAYGTCATC, AGTCA, TGACTCA, RSTGACTCMGW, ACSMGGAAGTR, RASRMGGAAGTR, GAMCCGGAAGTR, AACRAGGAAGTR, ASRAGGAAGTR, AYWTCCKK, YYWRRGGTCAAAGGTCAHVBD, AASTRGGTCACSGTGACCYACWT, WASYRGGKCAAAGKTCA, WGAMCTTTGACCY, AGGTCAG, AWSTRGGKCAAAGGKCA, YYWRRGGTCAAAGGTCAYMK, STRGGTCACSGTGACCYACW, TRGGTCACSGTGACCYACW, AWSTRGGTYAST, MRRGGKYAAWRGGTCAC, AANNNAGGTCANNGGNCA, AANNAGGTNANNGGTCA, AAANNAGGTCA, TGNCNNNTGACCTNNNTT, TGACCTNNNTT, ARRGGTCAAAGGTCAH, RRGGTCAAAGGTCA, CWRAWCYAGGYCAWAGKTCA, YMRGGTCATWGGGGTSARG, TGACCTY, RGGTCARAGGTCA, AWGTRGGTCAAAGGTCAT, AWGTRGGTCAAAGGTCA, ARRGGTCRTGACCYYT, DGRGGTCAAAGGTCRY, ARRGGTCGYGACCYYK, MSTGWCCTB, RGGTCAR, AAAAGGTCAM, RAGGTCAAAAGGTCAM, RAGGTCRTGACCTY, AAAAGGTCAH, RAGGTCAAAAGGTCAH, RAGGTCRTGACCT, CCAGGTGG, GCCACCTGSCTGYD, CCACCTGCMN, DRCAGGTGYR, RCAGGTG, ARCAGGTGCA, RRCAGGTGYR, RRCAGGTGCR, YCAGGTG, KCACCTGM,SSSRSCKCACCTGS, CACCTGSRK, RRCAGGTGY, AYGCACCTGTMRY, GCACCTGT, WWWMRAKRCACCTGYTAKWHAW, TTCCCRKAA, DAWTTCYWGGAAWYH, TTCCCRGAAWTBSKWTWCCKRGRR, YAWTTCYW, SWYTTCYW, KRYWYTTCYKRGA, RSWTTTCTARGAA, TTCYYRGAAAY, TTTCYKRGAAW, KAWTTCYTGGAAWTY, RAWTTCCARGAAWTM, TTTCYKRGAAA, TTCYYAGGAAWYT, TTCCNGGAA, TTCCTGGAA, CCNNGGAANNNNNA, TTCC, GGAANNNNNA, TTCNNGG.

255. DNA sequences in Claim 1, which are comprised of at least two of the following sequences, HRACCACGTGGTYD, TASCACRTGTCW, GCCAYGYGSS, MRMGTRHCACGTGDYACKYK, CACGTGS, CCACSTGWCY, RACCACGTGSTC, KACCACGTGSYY, CASGTGGC, RGCCACGTGCC, GASCACGTGGY, RASCACGTGGT, SSCCACGTGCYS, CCACGTGC, CCACGTGAA, CGTGG, CACGTGC, CGTGC, GCACGTGCT, YMCCACGTGYMV, SSSCACGYGS, CCACGTGS, SGCCACGTGGCS, CCACGTGG, GGCACGTGKY, SCACGTGS, RRMCACGTGR, CCACGTG, SVRTGASTCAKCM, GACTCAWKSKB, TGACTCAD, TGAGTCAK, TGACTCAB, GRTGACGTCAYC, GRTGAWTCAYC, ATGAYRCG, ATGAYRCG, KATGASTCAYM, DRTGACTCATY, RRTGASTCAKS, KKRTGACTCATMM, DRATGACTCATHY, ATGACTCAT, RTGACTCAT, YKRTGACTMATMC, RRTGACTMAT, RTGACGYMAY, TGASTCAYCH, RTGACTCAYYC, KRRTGASTCAB, GRTGACGTMAT, RRTGASTCAB, RTGAGTCAY, RTGACGTMAT, RTGASTCA, KRTGASTCAY, KRTGACGTCAYM, KKRTKACGTCAYCGC, KKRTGAGTCAYM, KRTGASTCAYMV, KKRTGAGTCAYMV, RTGAGTCAYM, DRTGACGTCATMMKTY, TGAMTCA, TGACTCAK, KKWATGASKCATMY, RTGAGTCAYCS, DVTGASTCATB, BGATGACGTCATCR, TGASTCAT, ATGACGTCATCR, ATGACGTCAYC, GATGAYGTCATC, AGTCA, TGACTCA, RSTGACTCMGW, ACSMGGAAGTR, RASRMGGAAGTR, GAMCCGGAAGTR, AACRAGGAAGTR, ASRAGGAAGTR, AYWTCCKK, YYWRRGGTCAAAGGTCAHVBD, AASTRGGTCACSGTGACCYACWT, WASYRGGKCAAAGKTCA, WGAMCTTTGACCY, AGGTCAG, AWSTRGGKCAAAGGKCA, YYWRRGGTCAAAGGTCAYMK, STRGGTCACSGTGACCYACW, TRGGTCACSGTGACCYACW, AWSTRGGTYAST, MRRGGKYAAWRGGTCAC, AANNNAGGTCANNGGNCA, AANNAGGTNANNGGTCA, AAANNAGGTCA, TGNCNNNTGACCTNNNTT, TGACCTNNNTT,ARRGGTCAAAGGTCAH, RRGGTCAAAGGTCA, CWRAWCYAGGYCAWAGKTCA, YMRGGTCATWGGGGTSARG, TGACCTY, RGGTCARAGGTCA, AWGTRGGTCAAAGGTCAT, AWGTRGGTCAAAGGTCA, ARRGGTCRTGACCYYT, DGRGGTCAAAGGTCRY, ARRGGTCGYGACCYYK, MSTGWCCTB, RGGTCAR, AAAAGGTCAM, RAGGTC AAAAGGTCAM, RAGGTCRTGACCTY, AAAAGGTCAH, RAGGTCAAAAGGTCAH, RAGGTCRTGACCT, CCAGGTGG, GCCACCTGSCTGYD, CCACCTGCMN, DRCAGGTGYR, RCAGGTG, ARCAGGTGCA, RRCAGGTGYR, RRCAGGTGCR, YCAGGTG, KCACCTGM, SSSRSCKCACCTGS, CACCTGSRK, RRCAGGTGY, AYGCACCTGTMRY, GCACCTGT, WWWMRAKRCACCTGYTAKWHAW, TTCCCRKAA, DAWTTCYWGGAAWYH, TTCCCRGAAWTBSKWTWCCKRGRR, YAWTTCYW, SWYTTCYW, KRYWYTTCYKRGA, RSWTTTCTARGAA, TTCYYRGAAAY, TTTCYKRGAAW, KAWTTCYTGGAAWTY, RAWTTCCARGAAWTM, TTTCYKRGAAA, TTCYYAGGAAWYT, TTCCNGGAA, TTCCTGGAA, CCNNGGAANNNNNA, TTCC, GGAANNNNNA, TTCNNGG, where one is added before the promoter driving expression of the therapeutic gene and another is added after the PolyA signal of the therapeutic gene.

256. DNA sequences in Claim 1, which are comprised of at least two of the following sequences, HRACCACGTGGTYD, TASCACRTGTCW, GCCAYGYGSS, MRMGTRHCACGTGDYACKYK, CACGTGS, CCACSTGWCY, RACCACGTGSTC, KACCACGTGSYY, CASGTGGC, RGCCACGTGCC, GASCACGTGGY, RASCACGTGGT, SSCCACGTGCYS, CCACGTGC, CCACGTGAA, CGTGG, CACGTGC, CGTGC, GCACGTGCT, YMCCACGTGYMV, SSSCACGYGS, CCACGTGS, SGCCACGTGGCS, CCACGTGG, GGCACGTGKY, SCACGTGS, RRMCACGTGR, CCACGTG, SVRTGASTCAKCM, GACTCAWKSKB, TGACTCAD, TGAGTCAK, TGACTCAB, GRTGACGTCAYC, GRTGAWTCAYC, ATGAYRCG, ATGAYRCG, KATGASTCAYM, DRTGACTCATY, RRTGASTCAKS, KKRTGACTCATMM, DRATGACTCATHY, ATGACTCAT, RTGACTCAT, YKRTGACTMATMC, RRTGACTMAT, RTGACGYMAY, TGASTCAYCH, RTGACTCAYYC, KRRTGASTCAB, GRTGACGTMAT, RRTGASTCAB, RTGAGTCAY, RTGACGTMAT, RTGASTCA, KRTGASTCAY, KRTGACGTCAYM, KKRTKACGTCAYCGC, KKRTGAGTCAYM, KRTGASTCAYMV,KKRTGAGTCAYMV, RTGAGTCAYM, DRTGACGTCATMMKTY, TGAMTCA, TGACTCAK, KKWATGASKCATMY, RTGAGTCAYCS, DVTGASTCATB, BGATGACGTCATCR, TGASTCAT, ATGACGTCATCR, ATGACGTCAYC, GATGAYGTCATC, AGTCA, TGACTCA, RSTGACTCMGW, ACSMGGAAGTR, RASRMGGAAGTR, GAMCCGGAAGTR, AACRAGGAAGTR, ASRAGGAAGTR, AYWTCCKK, YYWRRGGTCAAAGGTCAHVBD, AASTRGGTCACSGTGACCYACWT, WASYRGGKCAAAGKTCA, WGAMCTTTGACCY, AGGTCAG, AWSTRGGKCAAAGGKCA, YYWRRGGTCAAAGGTCAYMK, STRGGTCACSGTGACCYACW, TRGGTCACSGTGACCYACW, AWSTRGGTYAST, MRRGGKYAAWRGGTCAC, AANNNAGGTCANNGGNCA, AANNAGGTNANNGGTCA, AAANNAGGTCA, TGNCNNNTGACCTNNNTT, TGACCTNNNTT, ARRGGTCAAAGGTCAH, RRGGTCAAAGGTCA, CWRAWCYAGGYCAWAGKTCA, YMRGGTCATWGGGGTSARG, TGACCTY, RGGTCARAGGTCA, AWGTRGGTCAAAGGTCAT, AWGTRGGTCAAAGGTCA, ARRGGTCRTGACCYYT, DGRGGTCAAAGGTCRY, ARRGGTCGYGACCYYK, MSTGWCCTB, RGGTCAR, AAAAGGTCAM, RAGGTCAAAAGGTCAM, RAGGTCRTGACCTY, AAAAGGTCAH, RAGGTCAAAAGGTCAH, RAGGTCRTGACCT, CCAGGTGG, GCCACCTGSCTGYD, CCACCTGCMN, DRCAGGTGYR, RCAGGTG, ARCAGGTGCA, RRCAGGTGYR, RRCAGGTGCR, YCAGGTG, KCACCTGM, SSSRSCKCACCTGS, CACCTGSRK, RRCAGGTGY, AYGCACCTGTMRY, GCACCTGT, WWWMRAKRCACCTGYTAKWHAW, TTCCCRKAA, DAWTTCYWGGAAWYH, TTCCCRGAAWTBSKWTWCCKRGRR, YAWTTCYW, SWYTTCYW, KRYWYTTCYKRGA, RSWTTTCTARGAA, TTCYYRGAAAY, TTTCYKRGAAW, KAWTTCYTGGAAWTY, RAWTTCCARGAAWTM, TTTCYKRGAAA, TTCYYAGGAAWYT, TTCCNGGAA, TTCCTGGAA, CCNNGGAANNNNNA, TTCC, GGAANNNNNA, TTCNNGG, which are separated by at least 6 nucleotides.

257. DNA in Claim 1, which is linear double stranded DNA.

258. DNA in Claim 1, which is linear single stranded DNA.

259. DNA in Claim 1, which is circular double stranded DNA.

260. DNA in Claim 1, which is circular single stranded DNA.

261. DNA in Claim 1, which is partially double stranded DNA.

262. DNA in Claim 1, which is a DNA-RNA hybrid.

263. DNA in Claim 1, which is a DNA-peptide hybrid.

264. DNA in Claim 1, which is a synthetically modified DNA or DNA hybrid.

265. DNA in Claim 1, which is comprised of chemically modified and unmodified DNA.

266. Treatments in Claim 1 which are intended for human pathologies.

267. Treatments in Claim 1 which are intended for animal pathologies.

268. Treatments in Claim 1 which are intended for mammalian pathologies.

269. Treatments in Claim 1 which are intended for augmentation of gene expression, which is reduced as a function of aging.

270. Treatments in Claim 1 which are intended for the replacing of missing or non-functioning genes.

271. Treatments in Claim 1, which are intended for the alleviation of pathologies caused by metabolic diseases.

272. Treatments in Claim 1, which are intended for the alleviation of pathologies caused by musculoskeletal diseases.

273. Treatments in Claim 1, which are intended for the alleviation of pathologies caused by cardiovascular diseases.

274. Treatments in Claim 1, which are intended for the alleviation of pathologies caused by diseases of the central and / or peripheral nervous systems.

275. Treatments in Claim 1, which are intended for the alleviation of pathologies in autoimmune diseases.

276. Treatments in Claim 1, which are intended for the alleviation of pathologies caused by infectious diseases.

277. Treatments in Claim 1, which are intended for the alleviation of pathologies caused by environmental conditions.

278. Treatments in Claim 1 which are intended for genome modification, silencing, or otherwise altering the genome or level of expression.

279. Each and all of the constructs in the Examples section.

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