He aha te Hangarau Paturopi?

Mā te āwhina o te hangarau paturopi, kua taea te whakarerekē i te rahi ngota ngota, te pharmacokinetics, te immunogenicity, te hononga here, te motuhaketanga me te mahi a te kaiwhakawhiwhi o ngā paturopi. I muri i te hanga paturopi, mā te here motuhake o ngā paturopi ka tino whai hua rātou i roto i te tātaritanga haumanu me te maimoatanga. Mā te hangarau paturopi, ka taea e rātou te whakatutuki i ngā hiahia o te whanaketanga wawe o te rongoā me te tātaritanga.

Ko te whāinga o te hangarau paturopi he hoahoa me te whakaputa i ngā mahi tino motuhake, pumau e kore e taea e ngā paturopi taiao te whakatutuki, ā, koinei te pūtake mō te whakaputanga o ngā paturopi rongoā.

Me ōna wheako kaupapa whānui i roto i te hangarau paturopi, ka taea e Alpha Lifetech te whakarato ratonga paturopi monoclonal me polyclonal kua whakaritea mō ngā momo maha, tae atu ki te hanga whare pukapuka paturopi whakaaturanga phage me ngā ratonga tirotiro. Ka taea e Alpha Lifetech te whakarato ki ngā kiritaki he paturopi biosimilar kounga me ngā hua pūmua recombinant, me ngā ratonga e rite ana, hei whakaputa paturopi whai hua, tino motuhake, me te pumau. Mā te whakamahi i ngā tūāpapa paturopi whānui, pūmua me ngā pūnaha whakaatu phage, ka whakaratohia e mātou ngā ratonga e kapi ana i te taha whakarunga me te taha whakararo o te hanga paturopi, tae atu ki ngā ratonga hangarau pēnei i te whakatangatatanga paturopi, te purenga paturopi, te raupapatanga paturopi, me te whakamana paturopi.

Ko te wāhanga matua o te hangarau paturopi e pā ana ki ngā hangarau e rua:

--Hangarau DNA Whakahou

--Hangarau Hybridoma

Ko te tere o te whanaketanga o te hangarau paturopi e pā ana ki ngā hangarau nui e toru:

--Te hangarau tārua ira me te tauhohenga mekameka polymerase

--Te whakaputanga pūmua: Ka hangaia ngā pūmua recombinant e ngā pūnaha whakaputanga pērā i te rewena, ngā huaketo āhua-tokotoko, me ngā tipu

--Hoahoa hanganga āwhina rorohiko

I whakatāngatahia te whakatupuranga tuatahi o ngā paturopi hei hanga paturopi chimeric, i reira i honoa ai te rohe rerekē o ngā paturopi monoclonal kiore ki te rohe pumau o ngā ngota IgG tangata. I whakatōkia te rohe here antigen (CDR) o te paturopi monoclonal kiore whakatupuranga tuarua ki roto i te IgG tangata. Haunga te rohe CDR, ko ngā paturopi katoa he tata ki ngā paturopi tangata, ā, i whakapau kaha kia kore ai e puta he urupare paturopi anti-kiore tangata (HAMA) i te wā e whakamahia ana ngā paturopi clone kiore mō te maimoatanga tangata.

 

Hei hanga i tētahi whare pukapuka whakaatu phage, ko te taahiraa tuatahi ko te tiki i ngā ira e whakamārama ana i ngā paturopi, ka taea te wehe mai i ngā pūtau B o ngā kararehe kua āraihia (hanga whare pukapuka ārai mate), ka tangohia tika mai i ngā kararehe kāore i āraihia (hanga whare pukapuka tūturu), ka huihuia rānei i roto i te vitro me ngā kongakonga ira paturopi (hanga whare pukapuka hangai). Kātahi ka whakanuia ngā ira e te PCR, ka whakaurua ki roto i ngā plasmid, ka whakaatuhia ki roto i ngā pūnaha manaaki e tika ana (whakaaturanga rewena (ko te tikanga ko Pichia pastoris), te whakaaturanga prokaryotic (ko te tikanga ko E. coli), te whakaaturanga pūtau mammalian, te whakaaturanga pūtau tipu, me te whakaaturanga pūtau pepeke kua pangia e ngā huaketo āhua-tōka). Ko te mea tino noa ko te pūnaha whakaaturanga E. coli, e whakauru ana i tētahi raupapa paturopi whakamārama motuhake ki runga i te phage me te whakamārama i tētahi o ngā pūmua anga phage (pIII, pVIII rānei). Ko te whakakotahitanga ira o, ā, ka whakaaturia ki runga i te mata o ngā bacteriophage. Ko te kaupapa matua o tēnei hangarau ko te hanga i tētahi whare pukapuka whakaatu phage, he painga ki ngā whare pukapuka tūturu nā te mea ka taea e ia te here motuhake. Muri iho, ka tirotirohia ngā paturopi he motuhake ki te antigen mā te tukanga kōwhiri koiora, ka whakapūmauhia ngā antigen ūnga, ka horoia atu ngā phage kāore i herea, ā, ka horoia atu ngā phage kua herea hei whakarei ake. I muri i ngā huringa e toru, neke atu rānei, o te tāruaruatanga, ka wehea ngā paturopi he tino motuhake me te tino piripono.

Pikitia 3: Te Hanganga me te Tirotiro i te Whare Pukapuka Paturopi

Ka taea te whakamahi i te hangarau DNA recombinant hei whakaputa i ngā kongakonga paturopi. I te tīmatanga, ka taea anake te whakawhaiti i ngā paturopi Fab e te protease puku hei whakaputa i ngā kongakonga e rua (Fab'), kātahi ka nakunaku e te papain hei whakaputa i ngā kongakonga Fab takitahi. Ko te kongakonga Fv he mea hanga mai i te VH me te VL, he iti nei te pumau nā te korenga o ngā here disulfide. Nō reira, ka honoa ngātahitia a VH me VL mā roto i tētahi peptide poto o ngā waikawa amino 15-20 hei hanga i tētahi paturopi kongakonga taurangi mekameka kotahi (scFv) me te taumaha ngota o te 25KDa.

Nā te rangahau i te hanganga o te paturopi i roto i ngā Camelidae (Camel, LIama, me Alpaca) kua whakamāramahia ko ngā paturopi he mekameka taumaha anake, kāore he mekameka māmā, nō reira ka kiia rātou he paturopi mekameka taumaha (hcAb). Ko te rohe rerekē o ngā paturopi mekameka taumaha ka kiia he paturopi rohe kotahi, he nanobodies rānei, he VHH rānei, me te rahi o te 12-15 kDa. Hei monomers, kāore he here disulfide, ā, he tino pumau, he tino kaha te hononga ki ngā antigens.

Pikitia 5: Paturopi mekameka taumaha me te VHH/Nanobody

Ka whakamahia e te whakaputanga kore pūtau te whakaputanga o te DNA tūturu, hangai rānei hei whakatutuki i te hanga pūmua in vitro, mā te whakamahi i te pūnaha whakaputanga E. coli. Ka tere te whakaputa pūmua, ā, ka karo i te taumahatanga pākia me te paitini pūtau i runga i ngā pūtau ina whakaputahia he nui o ngā pūmua recombinant in vivo. Ka taea hoki e ia te whakaputa pūmua he uaua ki te hanga, pērā i ngā mea he uaua ki te whakarerekē i muri i te whakamāoritanga, te hanga rānei i ngā pūmua membrane.