
zink finger nuclease

zink-finger nucleases (zed. eff. aine. ess.) heey zink finger dii. aine. aii.-binding domenla dii. aine. aii.-cleavage domenmadhye misaloon tayar honare krutrim pratibandh enzymes aahet. zink finger domain vishisht ichchit dii. aine. aii. anukramanna lakshya karnyasathi tayar kele jaau shakatat aanee yamule zink-finger nucleusesna jatil genomemadhil adviteey anukramanna lakshya karnyas saksham karate. antarjanit dii. aine. aii. durusti yantrancha laabh gheuun, yaa abhikarmakancha vapar uchch jivanchya janukanmadhye achook badal karnyasathi keela jaau shakato. chrisper/cass 9 aanee tallens, zdfn heey genome editingchya kshetratil eka pramukh sadhan aahe.
kshetra.
dii. aine. aii.-bandhan kshetra.
vaiyaktik zed. eff. aine. chya dii. aine. aii.-binding domenmadhye samanyatah teen teey sahaa vaiyaktik zink botanchya punaravrutti asatat aanee pratyek 9 teey 18 basepareschya darmyan olakhoo shakatat. jarr zink finger domain 3 basepayer dna kram purnapane olakhatat, tarr teey 3-finger arrey tayar karoo shakatat jeey 9 basepayer lakshya sthal olakhoo shakatat. itar prakriya, sahaa kinwa adhik vaiyaktik zink botanni zink-finger arrey tayar karnyasathi ektar 1-boat kinwa 2-botanche modules vaparu shakatat. yaa prakriyetil mukhya kamatarata mhanje vaiyaktik zink botanchi vishishtata overlap houu shakate aanee aaspaschya zink botanchya aanee dii. aine. aii. chya sandarbhavar avalambun asoo shakate. yaa "sandarbh avalambitva" chaa hishob karnyachya paddhatinshivay, manak modular assembly prakriya anekada ayashasvi hote.
ichchit anukram lakshyit karnyas saksham asalelya zink-finger arrey tayar karnyasathi nivad karnyachya anek paddhati vaparlya gelya aahet. prarambhik nivad prayatnanmadhye anshatah yadruchchik zink-finger arrechya mothya poolmadhun dilelya dii. aine. aii. lakshyala bandhanari prathine nivadanyasathi fages displaycha vapar keela gela. alikadchya prayatnanmadhye yeast vann-hibrid pranali, bacteria vann-hibrid aanee too-hibrid pranali aanee sastan pranyanchya peshi yancha vapar karnyat aala aahe. naveen zink-finger arrey nivadanyasathi eka aashadayak naveen paddhat jivanuyukt done-sankarit pranalicha vapar karate aanee tyachya nirmatyanni teela 'open' asey naav dile aahe. hii pranali vaiyaktik zink botanche purv-nivadalele pool ekatra karate jeey pratyekane dilelya tiheri botanna bandhanyasathi nivadle hote aanee nantar ichchit 9-bii. pii. anukram bandhanyas saksham asalelya 3-botanchya sarani midvinyasathi nivadichya dusya fericha vapar karate. hii pranali jast-botanchya sanghadvare abhiyantriki jast-botanchya saranjamanchya vyavsayik strotanna paryay mhanoon vikasit kelee gelee hotee.
dii. aine. aii.-cleavage kshetra.
aay. aay. ess. nirbandh endonucles phoki prakaratil vishisht nasalele vichhedan kshetra samanyatah zed. eff. aine. madhye vichhedan kshetra mhanoon vaparale jaate. 
dii. aine. aii. chee vichhedan karnyasathi heey vichhedan kshetra dvigunit karane aavashyak aahe 
aanee asha prakare naun-palyndromic dii. aine. aii. sthalanna lakshya karnyasathi zed. eff. aine. chee jodee aavashyak aahe. manak zed. eff. aine. heey clevage kshetrala pratyek zink finger kshetrachya see-terminshee jodatat. done clevage domenna dii. aine. aii. chee patali qamee aanee khandit karnyasathi, done vaiyaktik zed. eff. aine. neey dii. aine. aii. chya viruddha strandla tyanchya see-terminalpasoon vishisht antarachya antaravar bandhale pahije. zink finger domain aanee cleavage domain darmyan sarvat samanyatah vaparlya jaanarya linker sequencesathi pratyek bandhansthalachi 5 'dhaar 5 teey 7 bii. pii. neey vegali karane aavashyak aahe.
zed. eff. aine. madhye vaparlya jaanarya nuclease kshetrachi kriyashilata aanee vishishtata donhi sudharanyasathi anek bhinn prathine abhiyantriki tantre vaparali gelee aahet. nirdeshit utkranticha vapar vadhiv vichhedan kriyakalapansah phoki prakar tayar karnyasathi keela gela aahe jyala lekhakanni "sharkey" asey naav dile aahe. sanrachana-aadharit rachana dekhil dimerisation interfacemadhye badal karoon fokichi vichhedan vishishtata sudharanyasathi vaparali gelee aahe jenekarun keval ichchit heterodymeric prajati sakriy asateel.
anuprayog.
zink finger nucleuses heey arabidopsis, tambakhu, soyabean, makaa, "drosophila melanogaster", see. yasah anek vanaspati aanee pranyanchya genomemadhe ferfar karnyasathi upayukt aahet. elegans, "platineres dumerilly", see archin, 
resheem kidya, 
zebrafish, bedook, under, undeer, sase, dukkar, guredhore aanee 
sastan pranyanchya peshinche vividh prakar. haemophilia undaranchya pratikrutimadhye zink finger nucleagescha dekhil vapar keela gela aahe aanee vaidyakeey chachanimadhye zink finger nucleasesdware vyatyay aalelya see. see. aar. 5 janukasah see. dii. 4 + manvi tii-peshi etch. aay. vhee./edsasathi sambhavya upchar mhanoon surakshit asalyache aadhalale aahe. isogenic manvi rog models navachya anuvanshik rog modelschee naveen pidhi tayar karnyasathi dekhil zed. eff. aine. chaa vapar keela jaato.
elil nishkriy karane.
utparivarti elilmadhye dii. aine. aii. madhye duheri-strand break (dii. ess. bii. ess.) tayar karoon visham-sukshmajiv vyaktinmadhye prabhavi utparivartan aksham karnyasathi zed. eff. aine. chaa vapar keela jaau shakato (anuvanshik punarsanyojan pahaa), jeey samaroop namunyachya anupasthitit, gair-samaroop end-johning (aine. etch. eae. jeey.) dware durust kele jaeel. donhi tokanna ekatra jodoon enhage dii. ess. bii. chee durusti karate aanee sahasa konatehi utparivartan nirman karat nahee, jarr kaap swachchh aanee sope asel tarr. tathapi, kahee prakarananmadhye, durusti apoorn asate, parinami bases-payers kadhoon takane kinwa samavisht karane, frame-shift tayar karane aanee hanikarak prathinanche utpadan rokhane. janukeey anukramache sampoorn mothe bhag purnapane kadhoon taknyasathi dekhil zed. eff. aine. chya anek jodya vaparlya jaau shakatat.
sampadan kriyakalapavar laksh thevanyasathi, lakshya kshetracha pii. see. aar. donhi elil vadhavato aanee jarr tyat eka samavisht karane, hatvane kinwa utparivartan asel tarr tyacha parinam heteroduplex single-strand babalmadhye hoto joou cleavage parakh sahajpane shodhu shakato.
tiheri punaravrutti vikaranmadhye rog nirman karananya elilmadhye badal karnyasathi dekhil zed. eff. aine. chaa vapar keela gela aahe. vistarit cag/ctg punaravrutti marg haah huntington rog, myotonic dystrophy aanee anek spinocerabler attaxiass eka dozenhoon adhik varshane midalelya majjatantunchya vikaransathi anuvanshik aadhar aahe. manvi peshinmadhye heey dakhavun dile gele aahe qee zed. eff. aine. heey duheri-strand break (dii. ess. bii. ess.) thet cag punaravruttisathi nirdeshit karoo shakatat aanee punaravrutti lamb pathological lambipasoon lahan, qamee vishari lambiparyant sankuchit karoo shakatat.
alikadech, sanshodhakanchya eka gatane zebrafish bhrunatil goal rangdravya januk aanee aine. tii. ell. janukamadhye anuvanshik badal karnyasathi zed. eff. aine. tantradnyanacha yashasviritya vapar keela aahe. vishisht zink-finger motifs vegalya dii. aine. aii. anukram olakhanyasathi tayar karnyat aale hote. zed. eff. aine.-encoding emm. aar. aine. aii. eka-peshi bhrunamadhye injectiondware dile gele aanee pranyanchya uchch takkevarit ichchit utparivartan aanee phenotype hote. tyanchya sanshodhan karyane heey dakhavun dile qee zed. eff. aine. visheshtah aanee karyakshamatene jantu resheteel swarasya asalelya thikani aanuvanshik utparivarti elil tayar karoo shakatat aanee zed. eff. aine.-prerit eleelcha prasar pudhil pidhyanmadhye keela jaau shakato.
zebrafish bhrunamadhye vishisht utparivartan tayar karnyasathi zed. eff. aine. chaa vapar karnyache asech sanshodhan itar sanshodhan gatanni dekhil kele aahe. zebra mashanmadhil keey. dii. aar. januk heey raktavahinyanchya endothelial vadhicha ghatak-2 receptorsathi sanketan karate. yaa lakshyit thikani utparivartaniy jakhama aaplyatil sanshodhakanchya eka gatane zed. eff. aine. tantracha vapar karoon prerit kelya hotya. tyanni suchavale qee zed. eff. aine. tantra utparivartananchya lakshyit elelic malikechya saral nirmitila anumati dete; teey prajati-vishisht bhrun stame seela reshanchya astitvavar avalambun nasate aanee itar prushthavanshiy pranyanna lagoo hote, visheshtah jyanche bhrun sahaj upalabdh aahet; shevati, zebrafishmadhye lakshyit nock-inn sadhya karane dekhil vyavharya aahe, mhanoon aataparyant durgam asalele manvi rog model tayar karane shakya aahe.
elil sampadan.
zed. eff. aine. chaa vapar, puravile gelele dii. aine. aii. tukada template mhanoon vaparoon dii. ess. bii. durust karnyasathi samaroop punarsanyojan (etch. aar.) yantrasamagricha vapar karoon, eleelcha kram punha lihinyasathi dekhil keela jaato. etch. aar. yantrana kharab jhalelya gunasutra aanee atirikt-gunasutratil tukadyanmadhil samarupata shodhate aanee gunasutrachya done tutalelya tokanmadhil tukadyachya kramachi nakkal karate, tyaa tukadyat mool kram aahe qee nahee yachee parva naan karata. jarr vishay lakshya elilsathi samaroop asel tarr tantrachi karyakshamta qamee hote kaaran elilchi naan kharab jhaleli prat puravalelya tukadyapeksha durustisathi template mhanoon vaparali jaau shakate.
januk upchar.
januk upcharpaddhatiche yash heey peshinna ija naan pohochavata, oncogenic utparivartan naan karata kinwa rogpratikarak pratisad naan deta manvi genomemadhe yogya gunasutra lakshyit thikani upcharatmak janukanchya karyaksham antarbhavavar avalambun asate. plasmid vectorchi rachana sopee aanee saral aahe. zink-finger prathinansah (zed. eff. pii. ess.) 'phoke' aay endonuclease vishisht nasalele vichhedan kshetra (aine.) ekatra karnare sanukoolit-rachana kelele zed. eff. aine. heey genomemadhe site-vishisht dii. ess. bii. pohochavanyacha eka samanya marg detat aanee parimanachya anek kramane sthanik samaroop punarsanyojanala uttejan detat. yamule manvi peshinmadhye lakshyit januk sudharana kinwa janukeey rachana sampadan haah vyavharya paryay banato. zed. eff. aine.-encoding plasmidcha vapar manvi peshinmadhil vishisht januk sthanala dii. ess. bii. lakshya karnyasathi zed. eff. aine. kshanikpane vyakt karnyasathi keela jaau shakato, tyamule teey upcharatmak janukanchya purv-nivadalelya gunasutrachya thikani lakshyit vitaranasathi eka utkrusht marg detat. zed. eff. aine.-encoding plasmid-aadharit drushtikonat upcharatmak janukanchya vishanujanya vitaranasandarbhat asalelya serve samasyanna talhanyachi kshamata aahe. zed. eff. aine. chya pahilya upcharatmak anuprayoganmadhye rugnachya swatachya moolpeshincha vapar karoon "ex vivo" upcharpaddhati samavisht asanyachi shakyata aahe. stame seela genome sampadit kelyanantar, peshi sanvardhanamadhye vistarit kelya jaau shakatat aanee durust karyansah bhinn peshi tayar karnyasathi rugnamadhye punha samavisht kelya jaau shakatat. prarambhik lakshyanmadhye bahudha ekjanya roganchi karane samavisht aahet, jase qee januk sudharanyasathi il2rγ januk aanee β-globin januk aanee utparivartan aanee apangatvasathi ccr5 januk.
sambhavya samasya.
auph-target cleavage.
jarr zink botanche kshetra tyanchya lakshyit jagesathi purese vishisht nasel kinwa teey swarasya asalelya genomemadhe ekhadya adviteey thikanala lakshya karat nastil, tarr uddisht nasalelya phaat houu shakatat. asha lakshya nasalelya fatyamule durusti yantrasamagrila bharavun taknyasathi puresha duheri-pattyanchya viramanche utpadan houu shakate aanee parinami, gunasutranchi punarrachana aanee/kinwa peshi mrutyu houu shakato. lakshya nasalelya fatanyachya ghatana daata dnachya yadruchchik ektrikaranala dekhil protsahan deu shakatat.
done jawalchya 9-basepayer sthalanna lakshya karananya 3-botanchya zdfnsathi auph-target cleavage qamee karnyasathi done vegvegalya paddhati darshavilya gelya aahet.
itar gut 4,5 kinwa 6 zink botansah zdfn vapartat jeey lamb aanee bahudha durmil sthalanna lakshya karatat aanee asha zdfn saiddhantikdrushtya qamee lakshyit kriyakalap deu shakatat. 3-botanchya zed. eff. aine. chya jodichi aanee 4-botanchya zed. eff. aine. chya jodichi tulana kelyas 3-botanchya zed. eff. aine. sathee 31 sthananvar aanee 4-botanchya zed. eff. aine. sathee 9 sthananvar manvi peshinmadhye auph-target phaat aadhalali. see" chey sampoorn genome sequencing. elegansla '5-botanchya zdfnschya jodies sudharit' keval ichchit badal aanee sitevaryl hatvane 'zdfn siteshee sambandhit nahee' asey aadhalale jeey soochit karate qee zdfnschi hii jodee 'see' madheel adviteey sitela lakshya karnyas saksham hotee. eleganscha genome.
rogpratikarak shakti.
manvi sharirat anek paradeshi prathine takalya gelyanusar, upcharatmak ghatak aanee too sakriy asalelya peshinviruddha rogpratikarak pratisad milanyachi jokhim asate. prathine keval kshanikpane vyakt kelee jaane aavashyak asalyane, tathapi, jyaa velevar pratisad vikasit houu shakato too vel qamee aahe.
lioo aanee itar. anukrame zadnikesesla antarjan bii-kesin (see. ess. aine. 2) locus lakshya karane, samarupata-nirdeshit durustidware lysostaphine aanee manvi lysozyme januk jodanila uttejit karate aanee stravit lysostaphine gayee midvate.
shakyata.
vanaspati aanee pranyanchya janukanmadhye achookpane badal karnyachya kshamateche moolbhut sanshodhan, shetee aanee manvi upcharpaddhatinmadhye asankhya upayog aahet. antarjanit janukanmadhye badal karnyasathi zed. eff. aine. ess. chaa vapar karane heey paramparikpane eka katheen kaam rahile aahe, kaaran pramukhyane jast botanche kshetra tayar karnyache aavhan jeey ichchit anukramala puresha vishishtatesah lakshya karate. zink finger domenchya abhiyantrikichya sudharit paddhati aanee vyavsayik puravathadarakadun zed. eff. aine. chee upalabdhata yamule heey tantradnyan aata vadhatya sanshodhakanchya hatat padale aahe. anek gut abhiyantriki hoaming endonucleges itar prakarche abhiyantriki nucleuses dekhil vikasit karat aahet.
 aanee engineered tall effectorsvar aadharit nucleuses.
tall effector nucleases (tallence) visheshtah manoranjak aahet kaaran tall effectors abhiyantyasathi khoop sope disatat.
aanee manvi peshinmadhil antarjaniy sthanala lakshya karnyasathi telensacha vapar keela jaau shakato. parantu aajparyant konihi asha abhikarmakancha vapar karoon clonal peshi resha kinwa transgenic jivanchya vilgikaranabaddal nond keleli nahee. etch. aay. vhee. chya upcharanmadhye sambhavya vaparasathi ess. bii.-728-tii. mhanoon olakhalya jaananya zed. eff. aine. chya eka prakarachi chachani karnyat aalee aahe.
zink-finger nickes.
zink-finger nickes (zedfanicase) heey duheri-strand klivejsathi aavashyak asalelya zdfn diamermadhil eka zdfn monomerchi utprerak kriya nishkriy karoon tayar kele jaatat. zedfanicase heey strand-vishisht nicking kriyakalap "inn vitro" darshavtat aanee asha prakare dii. aine. aii. madhye atyant vishisht single-strand break pradan karatat. yaa ess. ess. bii. ess. dii. aine. aii. sathee tyach cellular yantranetun jaatat jyacha zed. eff. aine. ess. vapar karatat, parantu teey tyanchya lakshya nicking sitewar utparivartaniy nej durustichi lakshaniy qamee varanvarta darshavtat. hii ghat etch. aar.-madhyasth januk badalansathi purvagrah pradan karate. zedfanicase heey susanskrut manvi aanee pashudhan peshinmadhye lakshyit etch. aar. prerit karoo shakatat, jaree teey jyaa sambandhit zed. eff. aine. pasoon tayar kele gele hote tyapeksha qamee staravar asale taree kaaran aanuvanshik badalashivay nixchi durusti kelee jaau shakate. zed. eff. aine.-madhyasth januk badalanchi eka pramukh maryada mhanje aine. etch. eae. jeey. aanee etch. aar. durusti marganmadhil spardha. dii. aine. aii. daata rachana astitvat asali taree, zed. eff. aine. ess. dware prerit dii. ess. bii. nantar durustichi donhi yantrana sakriy kelee jaau shakatat. asha prakare, zedfanicase haah truti-pravan nej durustichya ulat dii. aine. aii. durustichya etch. aar. paddhatila anukool banavanyasathi eka paddhat abhiyantriki karnyacha pahila vajvi prayatna aahe. nej durusti qamee karoon, zedfanicases asha prakare lakshyachya baherchya avanchhit badalanche swaroop qamee karoo shakatat. zdfnsmadhun zedfanicase jyaa sahajatene midavata yetat, teey zedfanikesachya anukulatesambandhichya pudhil abhyasasathi aanee tyanchi qamee jhaleli aine. etch. eae. jeey. varanvarta kayam thevat, tyanchi lakshyit etch. aar. chee patali vadhavanyasathi eka uttam vyaspeeth pradan karate.