Inzira 7 Zambere Mubushakashatsi bwa Farumasi Muri 2018

 

Kuba uri munsi yigitutu cyinshi kugirango duhatane mubibazo byubukungu n’ikoranabuhanga bitoroshye, uruganda rukora imiti n’ibinyabuzima rugomba guhora rushya muri gahunda zabo za R&D kugirango rukomeze imbere yumukino.

Udushya two hanze tuza muburyo butandukanye kandi buturuka ahantu hatandukanye - kuva muri laboratoire za kaminuza, kugeza abikorera ku giti cyabo batangijwe n’ishoramari batangijwe n’amashyirahamwe y’ubushakashatsi ku masezerano (CROs). Reka tubone gusubiramo bimwe mubyerekezo byubushakashatsi bizaba “bishyushye” muri 2018 ndetse no hanze yarwo, hanyuma tuvuge muri make bamwe mubakinnyi bakomeye batwara udushya.

Umwaka ushize BioPharmaTrend yavuze muri makeinzira nyinshi zingenzibigira ingaruka ku nganda zikomoka ku binyabuzima, aribyo: guteza imbere ibintu bitandukanye bya tekinoroji yo guhindura gene (cyane cyane CRISPR / Cas9); gukura gushimishije mubice bya immuno-oncology (CAR-T selile); kwiyongera kwibanda kubushakashatsi bwa microbiome; gushimangira ubuvuzi bwukuri; iterambere ryingenzi mubuvumbuzi bwa antibiotique; umunezero ugenda wiyongera kubyerekeye ubwenge bwa artile (AI) bwo kuvumbura ibiyobyabwenge / iterambere; gukura kutavugwaho rumwe ariko byihuse mubice byurumogi rwubuvuzi; no gukomeza kwibanda kuri farumasi kwishora mubikorwa bya R&D yohereza hanze kugirango bagere ku guhanga udushya n'ubuhanga.

Hano hepfo ni ugukomeza iri suzuma hamwe nibindi bice byinshi byubushakashatsi byongewe kurutonde, hamwe nibisobanuro byagutse kubyerekezo byavuzwe haruguru - aho bikenewe.

1. Kwemeza ubwenge bwa artificiel (AI) na pharma na biotech

Hamwe nibisakuzo hirya no hino muri AI muri iki gihe, biragoye gutangaza umuntu uwo ari we wese ufite iyi nzira mu bushakashatsi bwa farumasi. Ariko, twakagombye kumenya ko ibigo bitwarwa na AI bitangira gukurura hamwe na farumasi nini nabandi bakinnyi ba siyanse yubuzima, bafite ubufatanye bwinshi bwubushakashatsi na gahunda zifatanije -hanoni urutonde rwibikorwa byingenzi kugeza ubu, nahanoni isubiramo rigufi ryibikorwa bimwe bigaragara mumwanya wa "AI yo kuvumbura ibiyobyabwenge" mumezi menshi ashize.

Ubushobozi bwibikoresho bishingiye kuri AI ubu buracukumburwa mubyiciro byose byo kuvumbura ibiyobyabwenge no kwiteza imbere - kuva mubucukuzi bwamakuru yubushakashatsi no gufasha mukumenyekanisha no kwemeza intego, kugeza gufasha kuzana ibice bishya byifashishwa hamwe nabakandida ibiyobyabwenge, no guhanura imitungo nibibazo byabo. Hanyuma, software ishingiye kuri AI ubu irashobora gufasha mugutegura synthesis ya chimique kugirango ibone inyungu zinyungu. AI ikoreshwa kandi mugutegura ibizamini byabanjirije ivuriro n’amavuriro no gusesengura amakuru y’ibinyabuzima n’ubuvuzi.

Kurenga intego yo kuvumbura ibiyobyabwenge, AI ikoreshwa mubindi bice byubushakashatsi, urugero, muri gahunda yo kuvumbura imiti ya fenotipiki - gusesengura amakuru yavuye muburyo bwo gusuzuma ibintu byinshi.

Hamwe nibyibanze byibanze kuri AI itangizwa no gutangiza ibiyobyabwenge bito bya molekile, hari kandi inyungu zo gukoresha ubwo buryo bwo kuvumbura ibinyabuzima niterambere.

2. Kwagura umwanya wimiti kubushakashatsi bwo kuvumbura ibiyobyabwenge

Igice cyingenzi muri gahunda ntoya yo kuvumbura ibiyobyabwenge bya molekile ni ubushakashatsi bwakozwe - kumenya izo molekile zitangirira gutangira urugendo rugana imiti igezweho (ni gake barokoka uru rugendo, nubwo) - binyuze muburyo bwiza bwo kwemeza, kwemeza no gupima.

Ikintu cyingenzi cyubushakashatsi bwakozwe ni uburyo bwo kugera ahantu hagutse kandi hifashishijwe imiti itandukanye ya molekile nka molekile kugirango uhitemo abakandida, cyane cyane kubushakashatsi bwibinyabuzima bushya. Urebye ko ibyegeranyo biriho byakozwe na farumasi byubatswe igice gishingiye ku gishushanyo gito cya molekile kigamije intego z’ibinyabuzima zizwi, intego nshya y’ibinyabuzima isaba ibishushanyo bishya n’ibitekerezo bishya, aho gutunganya cyane imiti imwe.

Nyuma yibi bikenewe, laboratoire yamasomo hamwe nisosiyete yigenga ikora imibare yububiko bwimiti irenze kure ibiboneka mubisanzwe uruganda rukora imiti. Ingero zirimo ububiko bwa GDB-17 bwa molekile ziboneka zirimo miliyari 166.4 naFDB-17ya miliyoni 10 ibice bisa na molekile hamwe na atome ziremereye zigera kuri 17;ZINK- ububiko bwubusa bwibicuruzwa biboneka mubucuruzi kugirango bisuzumwe neza, birimo molekile miliyoni 750, harimo miliyoni 230 muburyo bwa 3D bwiteguye guhagarara; hamwe niterambere rya vuba ryibintu byogushobora kuboneka Muburyo bwa AvailabLe (NYAKURI) Umwanya wa chimique na Enamine - miliyoni 650 za molekile zishobora gushakishwa binyuzeUmuyoboro NYAKURIsoftware, naMiliyoni 337 zishobora gushakishwa(kubisa) kuri EnamineStore.

Ubundi buryo bwo kubona imiti mishya imeze nkibikoresho byo gushakisha ubushakashatsi ni ugukoresha ikoranabuhanga rya ADN ryifashishijwe (DELT). Bitewe na "split-na-pisine" ya synthesis ya DELT, birashoboka gukora umubare munini wibintu muburyo buhendutse kandi bukoresha igihe (miriyoni kugeza kuri miliyari yibintu).Hanoni raporo yubushishozi kumateka yamateka, ibitekerezo, intsinzi, aho bigarukira, hamwe nigihe kizaza cya tekinoroji yububiko bwa ADN.

3. Kwibanda kuri RNA hamwe na molekile nto

Iyi ni inzira ishyushye mumwanya wo kuvumbura ibiyobyabwenge hamwe numunezero ugenda wiyongera: abize, abatangiza ibinyabuzima na societe yimiti baragenda bakora cyane kubijyanye na RNA, nubwo gushidikanya nabyo ari byinshi.

Mu binyabuzima bizima,ADNkubika amakuru yaporoteyinesynthesis naRNAikora amabwiriza yashizwe muri ADN iganisha kuri protein synthesis muri ribosomes. Mugihe ibiyobyabwenge byinshi bigamije kwibasira poroteyine zitera indwara, rimwe na rimwe ntibihagije guhagarika inzira ziterwa na virusi. Birasa nkuburyo bwubwenge bwo gutangira hakiri kare mugikorwa no kugira ingaruka kuri RNA mbere yuko poroteyine zanashiramo, bityo bikagira uruhare runini muburyo bwo guhindura genotype kuri fenotipi idashaka (kwigaragaza indwara).

Ikibazo nuko, RNA izwiho kwibasirwa na molekile ntoya - ni umurongo, ariko irashobora kugoreka, kugundagurana, cyangwa kwizirika kuri yo, igatanga imiterere yayo mumifuka ibereye ibiyobyabwenge. Uretse ibyo, bitandukanye na poroteyine, zigizwe na bine zubaka nucleotide gusa bituma byose bisa cyane kandi bigoye guhitamo intego ya molekile nto.

Ariko,umubare witerambere rya vubatekereza ko mubyukuri bishoboka guteza imbere ibiyobyabwenge bisa, biologiya ikora molekile ntoya yibasira RNA. Ubuvanganzo bushya bwa siyansi bwatumye RNA yihuta -byibuze ibigo icumigira gahunda zahariwe, zirimo farumasi nini (Biogen, Merck, Novartis, na Pfizer), hamwe na biotech yatangije nka Arrakis Therapeutics hamwe na a$ 38M Urukurikirane rw'uruzigamuri 2017, no Kwagura Ubuvuzi -$ 55M Urukurikirane A kare muri 2018.

4. Ubuvumbuzi bushya bwa antibiotike

Hariho impungenge zikomeje kwiyongera kwa bagiteri zirwanya antibiyotike - superbugs. Ni bo nyirabayazana w'impfu zigera ku 700.000 ku isi buri mwaka, kandi nk'uko guverinoma y'Ubwongereza ibigaragaza, iyi mibare irashobora kwiyongera ku buryo bugaragara - bagera kuri miliyoni 10 mu 2050. Indwara ya bagiteri ihinduka kandi igatera kurwanya antibiyotike yari isanzwe ikoreshwa neza, hanyuma igahinduka ntacyo bimaze hamwe nigihe.

Kwanduza antibiyotike zidafite ishingiro zo kuvura indwara zoroheje ku barwayi no gukoresha antibiyotike mu bworozi bw’amatungo bibangamira iki kibazo mu kwihutisha umuvuduko w’imihindagurikire ya bagiteri, bigatuma irwanya ibiyobyabwenge bifite umuvuduko uteye ubwoba.

Ku rundi ruhande, ivumburwa rya antibiotique ryabaye ahantu hadashimishije mu bushakashatsi mu bya farumasi, ugereranije no guteza imbere imiti 'ishoboka mu bukungu'. Birashoboka ko arimpamvu nyamukuru itera gukama umuyoboro wibyiciro bya antibiotique yubuvuzi, hamwe nanyuma yatangijwe hashize imyaka irenga mirongo itatu.

Muri iki gihe kuvumbura antibiyotike biragenda bishimisha bitewe n’impinduka zingirakamaro mu nteko ishinga amategeko, zitera farumasi gusuka amafaranga muri gahunda yo kuvumbura antibiyotike, ndetse n’abashoramari bashora imari - mu gutangiza ibinyabuzima biteza imbere imiti itanga antibacterial. Muri 2016, umwe muri twe (AB)yasuzumye uko imiti ya antibiotique ivumburwakandi yavuze muri make bamwe mubatangiye gutanga ikizere mumwanya, harimo Pharmaceuticals ya Macrolide, Iterum Therapeutics, Spero Therapeutics, Cidara Therapeutics, na Entasis Therapeutics.

Ikigaragara ni uko kimwe mubyashimishije vuba aha mumwanya wa antibiotique nikuvumbura Teixobactinn'ibigereranyo byayo mu 2015 n'itsinda ry'abahanga bayobowe na Dr. Kim Lewis, umuyobozi w'ikigo gishinzwe kuvumbura imiti igabanya ubukana muri kaminuza y’amajyaruguru y'uburasirazuba. Iri tsinda rishya rya antibiyotike rikomeye ryizera ko rishobora kwihanganira iterambere rya bagiteri zirwanya. Umwaka ushize, abashakashatsi bo muri kaminuza ya Lincoln bakoze neza verisiyo ya teixobactin, itera intambwe yingenzi.

Ubu abashakashatsi bo mu kigo cy’ubushakashatsi bw’amaso muri Singapuru berekanye verisiyo yimiti ishobora gukiza neza Staphylococcus aureus keratitis muburyo bwimbeba nzima; mbere yuko ibikorwa bya teixobactin byerekanwe muri vitro gusa. Hamwe nubu bushakashatsi bushya, teixobactin izakenera indi myaka 6-10 yiterambere kugirango ibe imiti abaganga bashobora gukoresha.

Kuva havumburwa teixobactin mu 2015, undi muryango mushya wa antibiotique witwa malacidine waribyagaragaye mu ntangiriro za 2018. Ubu buvumbuzi buracyari mubyiciro byabwo byambere, kandi ntabwo byateye imbere nkubushakashatsi buheruka kuri teixobactin

5. Kugaragaza fenotypic

Inguzanyo y'ishusho:SciLifeLab

Muri 2011 abanditsi David Swinney na Jason Anthonybyatangajwe ibisubizo by'ibyo babonyekubyerekeranye nuburyo imiti mishya yavumbuwe hagati ya 1999 na 2008 igaragaza ko mubyukuri imiti myinshi ya mbere ya mbere yo mu cyiciro cya mbere y’imiti mito ya molekile yavumbuwe hakoreshejwe isuzuma rya fenotipiki kuruta uburyo bushingiye ku ntego (imiti 28 yemewe vs 17) - na biranatangaje cyane urebye ko aribwo buryo bushingiye ku ntego bwari bwibanze cyane mu gihe cyavuzwe.

Iri sesengura rikomeye ryateje ubuzima bushya bwo kuvumbura imiti ya fenotipiki kuva mu 2011 - haba mu nganda z’imiti ndetse no muri za kaminuza. Vuba aha, abahanga muri Novartisyakoze isubiramouko ibintu bimeze muri iki gihe kandi byaje kugera ku mwanzuro w'uko, mu gihe amashyirahamwe y’ubushakashatsi bwa farumasi yahuye n’ibibazo byinshi hamwe n’uburyo bwa fenotipiki, hari umubare ugabanuka wa ecran zishingiye ku ntego no kwiyongera kwa fenotipiki mu myaka 5 ishize. Birashoboka cyane, iyi nzira izakomeza kurenga 2018.

Icy'ingenzi, usibye kugereranya gusa uburyo bwa fenotipiki nintego zishingiye ku ntego, hariho inzira igaragara yerekeza ku ngirabuzimafatizo zigoye cyane, nko kuva ku murongo w'uturemangingo tudapfa tujya mu ngirabuzimafatizo z'ibanze, ingirabuzimafatizo z'abarwayi, imico hamwe, n'imico ya 3D. Igeragezwa ryubushakashatsi naryo riragenda rirushaho kuba ingorabahizi, rirenze kure ibyasomwe bitandukanye bigamije kureba impinduka mubice bito, gusesengura ingirabuzimafatizo imwe ndetse no gufata amashusho.

6. Inzego (umubiri) -kuri-a-chip

Microchips ikurikiranye ningirabuzimafatizo zabantu zishobora guhindura iterambere ryibiyobyabwenge, kwerekana imiterere nubuvuzi bwihariye. Izi microchips, zitwa 'organ-on-chips', zitanga ubundi buryo bwo gupima inyamaswa gakondo. Ubwanyuma, guhuza sisitemu burundu nuburyo bwo kugira sisitemu yose "umubiri-kuri-chip" nziza yo kuvumbura ibiyobyabwenge no gupima abakandida ibiyobyabwenge no kwemeza.

Iyi myumvire ubu ni ikintu kinini mu kuvumbura ibiyobyabwenge no mu mwanya w’iterambere kandi tumaze gusuzuma uko ibintu bimeze ndetse n’imiterere ya paradizo ya “organ-on-a-chip” muri vuba ahamini-gusubiramo.

Mugihe gushidikanya kwinshi kwabayeho hashize imyaka 6-7, mugihe ibyerekanwe kumurima byavuzwe nababishishikariye. Uyu munsi ariko, abanenga bigaragara ko bari mu mwiherero wuzuye. Ntabwo ifite ibigo bishinzwe kugenzura no gutera inkunga gusayakiriye icyo gitekerezo, ariko ubu biragenda byiyongerabyemewenkurubuga rwubushakashatsi bwibiyobyabwenge na pharma na academiya. Sisitemu zirenga zibiri zigaragara muri sisitemu ya chip. Soma byinshi kubyerekeyehano.

7. Kwandika ibinyabuzima

Agace ka bioprinting tissue nu ngingo byumuntu biratera imbere byihuse kandi, nta gushidikanya, ni ejo hazaza h'ubuvuzi. Yashinzwe mu ntangiriro za 2016,Cellinkni imwe mu masosiyete ya mbere kwisi atanga bioink ya 3D icapwa - amazi atuma ubuzima niterambere ryingirabuzimafatizo zabantu. Ubu isosiyete ikora bioprints ibice byumubiri - izuru n'amatwi, cyane cyane mugupima ibiyobyabwenge no kwisiga. Icapisha kandi cubes zifasha abashakashatsi "gukina" hamwe ningirabuzimafatizo ziva mu ngingo zabantu nkumwijima.

Cellink iherutse gufatanya na CTI Biotech, isosiyete ikora ubuvuzi bwa medtech yo mu Bufaransa izobereye mu gukora uturemangingo twa kanseri, mu rwego rwo guteza imbere cyane ubushakashatsi bwa kanseri no kuvumbura ibiyobyabwenge.

Gutangiza biotech ukiri muto bizafasha cyane cyane CTI gusohora 3D kopi yibibyimba bya kanseri, mukuvanga bioink ya Cellink hamwe nicyitegererezo cya kanseri yumurwayi. Ibi bizafasha abashakashatsi kumenya uburyo bushya bwo kuvura ubwoko bwa kanseri bwihariye.

Ubundi gutangiza biotech iteza imbere tekinoroji yo gucapa 3D yo gucapa ibikoresho biologiya - isosiyete ikora spinout ya kaminuza ya Oxford, OxSyBio, iyogusa ufite umutekano £ 10mmu ruhererekane A inkunga.

Mugihe 3D bioprinting ari tekinoroji yingirakamaro cyane, irahagaze kandi idafite ubuzima kuko ireba gusa imiterere yambere yikintu cyacapwe. Uburyo bwateye imbere cyane ni ugushyiramo "igihe" nkurwego rwa kane muri bio-ibintu byacapwe (ibyo bita "4D bioprinting"), bikabasha guhindura imiterere cyangwa imikorere hamwe nigihe mugihe hashyizweho imbaraga zo hanze.Hanoni ubushishozi bushishoza kuri 4D bioprinting.

Gufunga icyerekezo

Ndetse hatabayeho kwibira muri buri cyerekezo cyo hejuru tumaze gusobanura, bigomba kugaragara ko AI izajya ifata igice cyibikorwa. Ibi bice byose bishya bya biofarma byahindutse amakuru manini. Iyi miterere ubwayo irinda uruhare rukomeye kuri AI, ikanamenyesha ko, nk'inyandiko yanditswe kuri iyi ngingo, ko AI igizwe n'ibikoresho byinshi, byisesengura n'umubare bigenda bihindagurika. Ikoreshwa rya AI mukuvumbura ibiyobyabwenge no gutezimbere hakiri kare nibyinshi bigamije guhishura uburyo bwihishe hamwe nimyanzuro ihuza ibitera n'ingaruka ubundi bitamenyekana cyangwa byumvikana.

Rero, igice cyibikoresho bya AI bikoreshwa mubushakashatsi bwa farumasi bigwa muburyo bukwiye munsi ya moniker ya "imashini yubwenge" cyangwa "kwiga imashini". Ibi birashobora kugenzurwa nubuyobozi bwabantu, nko mubyiciro hamwe nuburyo bwo kwiga bwibarurishamibare, cyangwa ntibigenzurwe mubikorwa byabo byimbere nko mubikorwa byubwoko butandukanye bwimikorere yimitsi. Ururimi hamwe nibisobanuro bitunganijwe hamwe nuburyo bushoboka bwo gutekereza neza (cyangwa fuzzy) nabyo bigira uruhare runini.

Kumva uburyo iyi mirimo itandukanye ishobora kwinjizwa muri disipuline yagutse ya “AI” ni umurimo utoroshye ababishaka bose bagomba gukora. Kimwe mu bibanza byiza byo gushakisha ibisobanuro nibisobanuro niUbumenyi bwa Data Hagatiportal na cyane cyane inyandiko zanditswe na Vincent Granville, usanzweasobanura itandukanirohagati ya AI, imashini yegamiye, kwiga byimbitse, n'imibare. Guhinduka muburyo bwa AI muri rusange nikintu cyingenzi mugukomeza kumenya cyangwa imbere ya biofarma iyo ari yo yose.


Igihe cyo kohereza: Gicurasi-29-2018
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