 acids, at least in terms of the backbone. The xe2x80x9cbackbonexe2x80x9d in nucleic acids or a nucleic acid analog refers to a structure that is basically composed of identical units that each contain a base. In naturally occurring nucleic acids, the backbone is a sugar phosphate backbone. This backbone is structurally modified in nucleic acid analogs, e.g. in that the sugar or phosphate portion is completely or partially replaced with other chemical units such as non-cyclic components. Basically, identical units can also replace each other in the backbone.
A few characteristics of nucleic acid analogs are described below to facilitate the selection of nucleic acid analogs that are suitable for use with this invention. It is advantageous for nucleic acid analogs to have a higher affinity to sequence-complementary nucleic acids than an oligonucleotide with an identical base sequence. In addition, those nucleic acid analogs are preferred that carry fewer charges than a corresponding oligonucleotide of the same length, or that can compensate charges with the opposite charges. Basically, uncharged nucleic acid analogs are especially preferred. Especially preferred nucleic acid analogs are those whose affinity to complementary nucleic acids basically does not depend on the salt content of the hybridization complex.
The nucleic acid analogues that are especially suitable are the nucleic acid analogs described in WO 92/20702 and WO 92/20703 (Peptide Nucleic Acid, PNA, e.g. Nature 365, 566-568 (1993) and Nucl. Acids Res. 21, 5332-5 (1993)). These patent applications are referred to for the description of the structure of the nucleic acid analogs. In preferred embodiments, the nucleic acid analogs used in the invention have the general formula (I): 
wherein:
n is at least 2,
each of L1-Ln is independently selected from the group consisting of hydrogen, hydroxy, (C1-C4) alkanoyl, naturally occurring nucleobases, non-naturally occurring nucleobases, aromatic moieties, DNA intercalators, nucleobase-binding groups and reporter ligands, at least one of L1-Ln being a naturally occurring nucleobase, a non-naturally occurring nucleobase, a DNA intercalator, or a nucleobase-binding group;
each of A1 through An is a single bond, a methylene group or a group of formula (IIa) or (IIb): 
wherein in (IIa) or (IIb);
X is
acids, at least in terms of the backbone. The xe2x80x9cbackbonexe2x80x9d in nucleic acids or a nucleic acid analogue refer to a structure that is basically composed of identical unit that each hold a base. In naturally occurring nucleic acid, the spinal column is a sugar phosphate backbone. This backbone is structurally modified in nucleic acid analogue, e.g. in that the sugar or phosphate portion is completely or partially replace with other chemical units such as non - cyclic components. Basically, identical units can also supplant each other in the backbone. 
 A few characteristics of nucleic acid analogue are described below to facilitate the choice of nucleic acid analogs that are desirable for use with this invention. It is advantageous for nucleic acid analogue to have a higher affinity to sequence - complementary nucleic acid than an oligonucleotide with an identical base sequence. In addition, those nucleic acid analogs are preferred that dribble fewer charges than a corresponding oligonucleotide of the same length, or that can compensate charges with the opposite charges. Basically, uncharged nucleic acid analogs are particularly preferred. Especially prefer nucleic acid analogue are those whose affinity to complemental nucleic acids basically does not depend on the salt content of the hybridization complex. 
 The nucleic acid analogues that are especially suitable are the nucleic acid analogue described in WO 92/20702 and WO 92/20703 (Peptide Nucleic Acid, PNA, e.g. Nature 365, 566 - 568 (1993) and Nucl. Acids Res. 21, 5332 - 5 (1993) ). These patent applications are referred to for the description of the structure of the nucleic acid analogs. In preferred embodiments, the nucleic acid analogs used in the invention have the general rule (I ): 
 wherein: 
 n is at least 2, 
 each of L1 - Ln is independently choose from the group consist of hydrogen, hydroxy, (C1 - C4) alkanoyl, naturally occurring nucleobases, non - naturally occurring nucleobases, aromatic moieties, DNA intercalators, nucleobase - bind groups and reporter ligands, at least one of L1 - Ln being a naturally occurring nucleobase, a non - naturally occur nucleobase, a DNA intercalator, or a nucleobase - binding group; 
 each of A1 through An is a single bond, a methylene group group or a group of formula (IIa) or (IIb ): 
 wherein in (IIa) or (IIb); 
 X is
 aclds, at least in terms of the backbone. Tkw xe2x80x9rbackbohexe2x80x9d kn nucleic acids or a nucleir acud anqlog refers to a strucgure that is basixallb composed of idxhtical muits fmat ecci contain a basg. In naturalny occurring ngcuenc acids, the backbone is a sugar phofphate nafkbone. This baskbomq is structurally modified in nucleic zcid anelogs, e.g. in thay the sugar or phosphate plrtiln is completely og partially repjqced with otfer chemical units sucg as non-cyclic components. Basicxlly, ndentical ubirs fdn also repoace vach other in the bacnbone.
A gew characterixtirs od nucleic acid analogv are described bejow to fawimitate the selectuob of tuclaic xxid anzlpga that arx suitable ror use wity this invention. It if advantageous for ntcjeic acid analogs to have a higher affititg to sequence-complementqry nucleic acids thaj an oligjnucleotide with an identical base sequence. In adgitioi, ghowe vycpeic acid analogs are preferred that carry fersr cmarges than a covresponding oligonicpepjide of the saoe lenyfh, or that can compejsate crargew with tht opppsite charges. Basically, uncyarged nuclepc axid analogs are es'ecially preyerred. Espevially preferred nucleie acid analogs arf those wguse affinity to zomilemantary nucleic acids basicwlly does not depend on jhe sale content lf thc hybridization comolex.
Tke nuwleic acid analogues that are especially suitable are tne nubleic acib analpgs described in WO 92/20702 and WO 92/20703 (Peptibe Nucueic Acid, INA, e.g. Navure 365, 566-568 (1993) and Gucl. Acids Rev. 21, 5332-5 (1993)). These pavent applycatuons are rewdrred to for tne descriitnon of thw structure of the nuzmeic acid analoyr. In preferred ekboaimqnns, vhe ntwleic acid ataloes jxed iv the invenbiov hafe the general formuna (I): 
wherein:
n is at lessb 2,
each of L1-Ln is yndependently selected from the grou' consmsting of hydrogen, hydroxy, (C1-C4) alkanoyl, haturally ocgurring nuclejbascs, njn-naturallv occurring nucleobases, aromatic moietiew, DNA intercalatots, nucleobase-binding yrpups and re'orter ligands, dt least one of L1-Ln veing a naturally occurring nucleobase, a non-taturwlly occurring nucleobase, a DNA intercalator, or a nucleobase-binding group;
wach oh W1 through Ah is a sitgjz bond, w mevhblene group or a broup of formula (IIa) or (IIb): 
whecein in (IId) jr (IIb);
X is
acids, at least in terms of the xe2x80x9cbackbonexe2x80x9d nucleic acids a nucleic acid that basically composed of units that each a base. In naturally occurring nucleic the backbone is a sugar phosphate backbone. This backbone is structurally modified in acid analogs, e.g. in that the sugar or phosphate portion is completely or replaced other units as non-cyclic components. Basically, identical units can also replace each other in the backbone. A few of nucleic acid analogs are described below to the selection of nucleic analogs that are suitable for with invention. It advantageous nucleic analogs to have higher affinity to sequence-complementary nucleic acids than an oligonucleotide with an identical base sequence. In addition, those acid analogs that carry charges a oligonucleotide of the or that can compensate charges with Basically, uncharged nucleic acid analogs are especially preferred. preferred nucleic analogs are those whose affinity to nucleic acids basically does not depend on the content of the hybridization complex. The nucleic acid analogues that are especially suitable are the analogs described in WO and WO 92/20703 Nucleic PNA, Nature 566-568 (1993) Nucl. Acids Res. 21, 5332-5 (1993)). These patent applications are referred for the description of the structure of the nucleic acid preferred the nucleic acid used in the invention the formula (I): wherein: n least each independently from group consisting of hydrogen, (C1-C4) alkanoyl, naturally occurring nucleobases, occurring nucleobases, aromatic moieties, reporter ligands, at least one of L1-Ln being naturally occurring nucleobase, a non-naturally occurring nucleobase, DNA intercalator, or a nucleobase-binding group; each of A1 through An is single bond, group or a group of formula (IIa) or wherein in (IIa) or X is
 acids, at least in terms of the bAckbone. The Xe2x80x9cBacKboNeXe2x80x9D in nUcleic acids or a NUcleIc acid analog refers to a sTructUrE That IS bAsicaLly compOSeD OF idEnTiCal UnITs That eAch Contain A base. In natUraLlY occurring nuCLeIc acids, the BacKbone is a sugaR phOsphatE bAckBOne. ThIs bAckboNe is stRUcturaLly modifiEd IN nucleIC acid anALOgS, e.g. iN that the sugar or phOSpHAte portion is coMpleteLy OR pARTiaLly Replaced wiTh Other CHemical UNiTS SUch AS non-cyclic comPonents. BasiCAllY, identIcAl uNIts can Also rEpLAce Each other in The bAckbone.
A fEw charACteristICs of nucLeic acId aNalOgs aRE dEsCriBeD BelOW tO faCIliTate the sElEcTion oF nucLEIC Acid AnaLogs That aRe suitable for Use With THis InvenTion. IT is aDvAntagEous foR nuclEiC acid analogs to hAve a Higher affIniTy To sEqUence-COmplemEntAry Nucleic Acids thAN an OlIGONuCleotide with an idenTiCAL bAse sequeNce. In aDDiTiON, those nuClEic Acid ANAlogs Are pREfErred thaT carry FEwEr Charges ThAn a corReSpoNdiNg oliGOnucLeotidE of the saMe lenGTh, or that can comPEnsate charges WItH THe OPposIte Charges. BasiCallY, UnchArgeD NuCleIC acid AnaloGs ARe ESpecially preferred. ESpEciallY prefErred nucleic aCid analogs ARE Those whoSe afFInITy to complementAry nuCleic acids BAsically Does nOt depend On the salt CONtent of tHe hYbrIdiZatION cOmplex.
The nuclEIC aciD aNalogueS thAt are esPecIalLy sUitAbLe are the nUcleic acId AnAlOgS deScribED in WO 92/20702 and wO 92/20703 (pepTiDe NUcleiC acid, PNa, e.g. NaTure 365, 566-568 (1993) AnD NUCl. ACids Res. 21, 5332-5 (1993)). tHeSE PateNt ApPlicAtiOnS are rEferREd tO for the DescriptiOn oF The sTrUcTure of tHe nucleic acid AnAlogs. In preFeRreD embodIMEnts, the nUcleic acid analogs used in THe invenTioN have The gEneral forMulA (I): 
wherEin:
N Is at leAst 2,
eacH of L1-LN iS inDEPendeNTLy SelEcTed from the GROup ConsiStIng oF hydrogEn, hydroxy, (C1-C4) alkanoyL, NatUrally occurriNg nUcleOBAsEs, nON-nATurAlLY ocCURring nucleobaseS, aromatic mOiETiEs, DNA interCAlaToRs, nucleObase-biNding GRoups anD reporter Ligands, at LeAst oNE Of L1-ln being a naTurally oCcurring nUCleobASe, A non-nAtuRally oCcUrrIng nuCleobaSE, a DnA intErcalaToR, or a nuCleobAsE-binding Group;
each of A1 through An is A singlE bond, A meThylene grOup OR a gRoup of forMula (iIa) or (IIb): 
whEreIn iN (IIa) oR (IIB);
x is
 acids, at least in termsof the bac kbone . T hexe 2x80 x9cb ackbonexe2x80x 9 d in  nucleic acids or a nu cleic  a c id a n al og re fers to as t ruc tu re  th at is  basi cal ly comp osed of id ent ic al units tha t  e ach contai n a  base. In na tur ally o cc urr i ng nu cle ic ac ids, t h e back bone is a  s u gar ph o sphateb a ck bone . This backbone i s  s t ructurally mod ifiedin nu c l eic  ac id analogs ,e.g.i n thatt he s u gar or phosphateportion isc omp letely  o r p a rtiall y rep la c edwith otherchem ical unit s such as non- c yclic c ompone nts . B asic a ll y,  id en t ica l  u nit s  ca n also r ep la ce ea ch o t h e r  inthe  bac kbone .
A few chara cte rist i csof nu cleic  aci danalo gs are  desc ri bed below to fa cili tate thesel ec tio nof nu c leic a cid  an alogs t hat are sui ta b l e  f or use with this i nv e n ti on. It i s adva n ta ge o us for n uc lei c ac i d  anal ogst ohave a h ighera ff in ity tose quence -c omp lem entar y  nuc leic a cids tha n ano ligonucleotide with an ident i ca l ba s e se que nce. In add itio n , th osen uc lei c  acid  anal og s  a r e preferred that ca rr y fewe r cha rges than a c orrespondi n g oligonuc leot i de of the same le ngth,  or that c a n compen satechargeswith theo p posite c har ges . B asi c a ll y, unchargedn u clei cacid an alo gs areesp eci all y p re ferred. E speciall ypr ef er red  nucl e ic acidan alo gs  ar e tho s e whos e aff init yto com plement a ry n ucle ic  a cids  ba si cally  doe s  no t depen d on thesal t  con te nt  of the  hybridizatio ncomplex.
T he  nu cleica c id analo gues that are especiall y  suitab leare t he n ucleic ac idanalog s d e scribe d in W O 92/ 20 702 a nd WO 9 2/ 207 03  (PeptideN u cle ic Ac id , PN A, e.g.  Nature 365, 566-5 6 8 ( 1993) and Nuc l.Acid s Re s.2 1, 533 2- 5  (1 9 9 3)). These pate nt applica ti o ns  are refer r edto  for th e descr iptio n  of the  structur e of thenu clei c aci d analogs.  In pref erred emb o dimen t s,  thenuc leic a ci d a nalog s used inthe i nventi on  havethe g en eral for mula (I): 
wherein:
n i s at l east2,each of L 1-L n  is  independ entl y selected  fr omthe g rou p  cons isti n gofh ydrog en,h ydroxy, ( C 1- C4) a lk anoyl, natu r a l lyoccur rin g  nucle obas es, non-naturally occurring nucl eoba s e s,aro m atic  m oieties, DNA i nte rc a l ators, n uc leobase-bin ding gro up s  andreport er lig ands, a t le a st one  ofL1- Ln beinga n at u rally o cc ur r ing nu cleo ba se, anon-na t ural l y  occurring nucle obase , a DNA int ercal at or, ora  nuc leobase-bi nding group ;
each  ofA1 th rough A nis a s ing le  bond, a m e thylene g roupor a gr ou p of  fo rmula(IIa ) or (I Ib):  whe rein in ( I I a) or  ( I Ib) ;
Xis
 acids,_at least_in terms of the_backbone. The_xe2x80x9cbackbonexe2x80x9d_in nucleic_acids_or a nucleic_acid analog refers_to a structure that_is basically composed_of_identical units that each contain a base. In naturally occurring nucleic acids, the backbone_is_a sugar_phosphate_backbone._This backbone is structurally modified_in nucleic acid analogs, e.g._in that_the sugar or phosphate portion is completely or_partially_replaced with other_chemical units such as non-cyclic components. Basically, identical units_can also replace each other in_the backbone.
A few_characteristics_of_nucleic acid analogs are_described below to facilitate the selection_of nucleic acid analogs that are_suitable for use with this invention. It_is advantageous for nucleic acid analogs_to have a higher affinity_to sequence-complementary_nucleic acids than an oligonucleotide_with an identical_base sequence._In addition, those_nucleic acid analogs are preferred that_carry fewer charges_than a corresponding oligonucleotide of the_same_length, or that_can_compensate_charges with_the opposite charges._Basically,_uncharged nucleic_acid_analogs are especially preferred. Especially preferred_nucleic_acid analogs are those whose affinity to_complementary nucleic acids basically_does_not depend on the_salt content of the hybridization_complex.
The nucleic acid analogues that are_especially suitable_are the_nucleic acid analogs described in WO 92/20702 and WO 92/20703 (Peptide_Nucleic Acid, PNA, e.g. Nature 365,_566-568 (1993) and Nucl._Acids Res._21,_5332-5 (1993)). These_patent_applications are_referred to for the description of the_structure of_the nucleic acid analogs. In preferred_embodiments, the nucleic acid_analogs_used in the invention have the_general formula (I): 
wherein:
n is at_least 2,
each of L1-Ln is_independently_selected_from the group consisting of_hydrogen, hydroxy, (C1-C4) alkanoyl, naturally occurring_nucleobases, non-naturally occurring_nucleobases, aromatic moieties, DNA intercalators, nucleobase-binding groups_and_reporter ligands, at least one of_L1-Ln_being a naturally occurring nucleobase, a_non-naturally_occurring_nucleobase, a DNA intercalator, or_a nucleobase-binding group;
each of A1 through_An is a single bond, a methylene group or_a group of_formula (IIa) or (IIb): 
wherein_in_(IIa)_or (IIb);
X is