Boitlamo ba lysosomal: Ntho ea bohlokoa ho Adc Lord Perc le Sirna Shootion ea ho sebetsa hantle ha a ntlafatse

Mantsoe a bohlokoa: ADC Linker, ho lokolloa ha chelete, sebete sa paysosome, ho tsitsipaola-Sirna, Sirna Sceck, Sirna Demosce, Hepatocyte LYSOSOS, TRATOMAMES, TRITOMAMES

Lihlahisoa tsa Iphase 

Kenyelletso

Tsoelo-pele e fumanehang ka biotherapetutic e tsamaisitse lintho tsa ho iphetola ha lithibelo tsa antibody - Leha a ne a shebile liphofu tse fapaneng le mechini ea ADC le Sirna e itšetlehile haholo kasebete se nyonyehangTikoloho, moobotsitso ba ho tsitsipanammeCatabolism ea lysolisongBapala likarolo tsa povital. Li-Systems tsa ADC, seliba se nepahetseng saADC Linker by Cathepsnin B-Ke-musperigian in ds8201a leGGFG - DXDLitsela-pele li ne li laoloaHo lokolloa ho lokolloa. Bakeng sa Sirna Therapetics, ho hlola litšitiso tsa Lysosomal ho bohlokoa bakeng sa ho hlokahalaSirna tlisoangmmeSirna Pholoso, haholo ho sebelisaSalnac-Sirnae kopanya sepheo seoHepatocyte Lysosomes. Tokomane ena e kopaneng e hlahloba litsela tsena tse tloaelehileng le mathata.

1. Adc Oversview le mehopolo ea bohlokoa

ADC ke sethethefatsi sa biotherapeutuc se kopanyang monognal antibody, moputso oa cytotox, le adc thard. Lenane lena la ADC le etselitsoe ho netefatsa tokollo e nepahetseng ea lefa, le chabile ho hokahana le lisele tse atlehileng. Ho lokolloa ho laoloang ho ikoahlaea ka mokhoa o hlakileng, moo ho tsitsipaola maqeba a bolotsana ho bolela botsitso bo nepahetseng. Sebakeng sena, Cathepsin B e qala ho sebetsa ka nako e nepahetseng ho ea ho memori ea Adc 1 Mohlala, DS8201A e pheta-pheta ggfg - DxD Mechanism ho fihlela ho lokolloa ha lefa pele ka har'a sebete sa lithethefatsi le chefo ea tsamaiso ea lithethefatsi.

ADC Linker le moputso oa ho lokolla menyako

Moralo oa li-adc linker ke tsa bohlokoa bakeng sa ho netefatsa khoele e laoloang. ADC Linker e susumetsoa ke maemo a ka har'a sebete a ngangisana, moo ho boloi se phetha karolo ea bohlokoa. Balekane ba tsitsitseng ba tsamaisana le li-Catabolism ba sebetsang, ba netefatsa hore enzyme joalo ka Cathepsin B e ka sebetsa hantle ADC. Boemong ba ho patala ho lokolloa, ADC Linker e tlameha ho lula e tsitsitse nakong ea ho potoloha, 'me ha e hloekisoe ha u kena ka har'a sebete sa kabe. Cleavage ena e kopantsoe ke Cathepsin B, eo e leng ea bohlokoa bakeng sa ho tsosa Catabolism. Ho feta moo, litsamaiso tse tsoetseng pele joaloka DS8201A le GGFG - DXD e nka monyetla oa Tikoloho ea Laver, 'me u koale ho boloka tšebeliso ea lithsosomal.

Ntle le Cathepsnin B, lithuse tse ling tsa li-cathesine tse kang cathepsin L, cathesin m, le cathepsin t Tsamaiso ea ts'ebetso ea lysosomal le tokollo ea lithethefatsi. Cathepsnin L e ngolisitsoe ka hohle bakeng sa ts'ebetso ea eona e matla ea tumello le karolo ea eona ea liprotheine tse mpefatsang, ka ho etsa joalo. Ka mokhoa o ts'oanang, cathepsmm, leha e ne e hlile e tšoants'oa, e nka karolo katings ea Catabolism 'me e ka eketsa tšebetso ea litlhase tse ling. Catheesn K, e tsejoang ka ho fetisisa bakeng sa ts'ebetso ea eona ea ho oa ha eona ka matla a bone, e ka boela ea hloekisa litholoana tsa pep. Ho fetisoa le ka linako tse ling mesebetsi ea litolisano ea li-enzyme tsena e thusa ho etsa bonnete ba hore li-mekers tsa Adc li hlophisitsoe hantle ka har'a lisele tsa sepheo ha li ntse li boloka botsitso ba tsamaiso ea tsamaiso. Patlisiso e 'ngoe ho kena lipakeng tsa li-cathepsnin B, Cathepsin L, Cathepsinm, le Cathepsin K Poletso e Ncha ea Sengoli ho ntlafatsa maemo a holimo ka bongata.

2. Sirna Therapetictics le Liphephetso tsa ho tlisa

Sebaka sa Sirna le ho kena ha Lysosomal

Lithethefatsi tsa Sirna li fana ka lintlha tse phahameng haholo ka tencing; Leha ho le joalo, phephetso e kholo e bontša hore Sirna o baleha lihlong. Kamora ho emisa andocytosis, karolo e kholo ea Sirna e hapiloe lysosomes le hepatocyte lysosomes, moo li-Cassolism tse potlakileng tse fumanehang ka har'aLysosomal acid phosphatase-Kopisa botsitso ba kopo le ho lebisa ho silika ea Sirna.

Mochini oa Galnac-Sirna e kopanya

Galnac-Sirna e kopanya ntlafatso ea Sirna ea Surna ka ho tsamaisa thepa ea Asiaglycoten ea AsiaGrotein, e khothalletsang endocystocyte e potlakileng. Hang ha litšitiso li ne li lula, li-conjugebo li lokela ho hlola litšitiso tsa masopo tsa Lysosomal ho etsa hore liqoso tse atlehang tsa sirna li pholohe. Likhatiso tsa lik'hemik'hale tse kang 2'-F, le lihlopha tsa phosphororoeate ho eketsehileng li sirelletsa Sirna sebakeng se thata sa sebete sa sebete sa sebete sa sebete se nang le thata tsa sebete se nang le bothata.

Sistimi ea litaba tsa metabolic le khetho ea Oligonucleotides

Joalo ka litlhaselo tsa sebopeho sa sebopeho sa sebopeho, palo ea sirna e hloka ho ba theko e phahameng ho vitra Metabolic e tsitsitseng nakong ea ntlafatso ea pele nakong ea pelehi. Lithuto tsena li lekola tšusumetso ea Catagolism ea Lysosolism le karolo ea phossosomal acid acid acid e litšila kahare ho li-Hepatocyte li-lysosomes. Khatiso e behiloe ho ntlafatsa phano ea Sirna le ho netefatsa khanya ea khanya ea SIRNA. Litsamaiso tse fapaneng tsa liteko tse kang Liver ea Lichelete, Libese tse ikhethileng, le li-Hessomes tse ikhethileng, le liphiri tsa mantlha - li hiriloe ho etsisa tikoloho ea kelello. Ntlafatsa botsitso ba lysososo ho theosa le liteko tsena ke senotlolo sa ho ntlafatsa ts'ebetso ea lithethefatsi tsa sirna.

3. Karolo e tloaelehileng ea li-lysosomes

Li-sebete tsa maketsetso

Maalo a maano a adc le Sirna a lula a fetohela ka Sebete ea Iysome - e le organelle ea bohlokoa bakeng sa ts'ebetso ea lithethefatsi le litšila tsa lithethefatsi. Ho Adc System, mealo e ngangisano e laoloang e kentsoeng ka payload ka Cathepsin B adc 1 Har'a lingaka tsa Sirna Kahoo, ho boloka botsitso bo phahameng ba ho boloka tokelo ea ho tsebahatsa letlapa le sebetsang bakeng sa Catabolism ea lefapha la ADC e laoloang le ho ntlafatsoa ha ADNA.

Li-modes tsa vitro le litsamaiso tsa metabolic

Ho ithuta ka bobeli ba ADC ho lokolloa le ho tsilatsila ba nang le botsitso, bafuputsi ba sebelisa mefuta e mengata ea vitro.BoqapiMehlala-e joalo ka sebete sa raselo tritosomes Ntle le moo, litsamaiso tsa lipatlisiso tsa metabolic ho kenyelletsa litsamaiso tsa Livers S9 Mefuta ena e totobatsa bohlokoa ba ho tsamaisana le Catabolism ea lysolisong le lysososal Acidase ea acid ea phispase ea ho boloka katleho e nepahetseng.

4. Maano a majabajaba a ntlafalitsoeng a ntlafalitsoeng

Katleho ea kalafo ea ADC le lithethefatsi tsa Sirna li itšetlehile ka ho tsilatsila le ho laola pula ea lingaboto. Bakeng sa adcDS82011le ggfg - litsamaiso tsa DXD) li bohlokoa. Bakeng sa kalafo ea Sirna, litheolelo tsa lik'hemik'hale tsa Galiac-Sirna li kopanya tšebetso ea phossosomal acid acid ea acid le Sirna ho phonyoha. Mokhoa o kopaneng o nkang tikoloho e ikhethang ea sebete e bohlokoa bakeng sa ho atleha ho atleha ho atleha.

Sephetho

Mekhoa ea phekolo ea ADC le Sirna e tobana le mathata a tloaelehileng kahare ho tikoloho e lerato ea Bover, moo ho tsitsitseng ha lysool le Catabolism e khethollang katleho ea bona. Systems ea ADC, haholo-holo DS8201 le GGFG - DXD, itšetleha ka precise adc linker tothesin b bakeng sa tokollo e sebetsang. Ka mokhoa o ts'oanang, Sirna ea Tsamaisa Salnac-Sirna o ile a boela a hlola a phapanyetsano ea lysosomal a acid acid acid acid ho fihlela sirna e sebetsa hantle. Ka ho sebetsana le mefuta ea vitro e kang tritosomes le mapheo a kopaneng ho fetola matla a ma-adc le sirna Therapeutic.