Lub Sijhawm Thiab Kev Sib Tw Ntawm Mini Npua Ua Ib Hom Tsiaj Loj Loj

Los ntawm anatomical thiab physiological foundations, cov npua me me qhia qhov zoo sib xws nrog tib neeg hauv lawv lub cev.mob plawv, tso zis, dermatological, thiab digestive systems. Npua tau siv rau hauv kev siv tshuaj,Pharmacokinetics (PK), toxicology, thiab kev ntsuam xyuas cov cuab yeej kho mob tau ntau xyoo. Txawm li cas los xij, ib txwm muaj npua hauv tsev 'loj loj tau ua rau muaj kev sib tw ua haujlwm, rau kev tsim cov tsiaj me me, lossis cov npua me me, uas yooj yim dua, nyab xeeb, thiab tus nqi ntau dua - zoo. Cov tsiaj me me xws li Yucatan, Hanford, Sinclair, thiab Gottingen. Tsis tas li ntawd, genetic engineered me me npua nqa tib neeg hnyav- saw 1, 4, thiab lub teeb- saw κ noob tau tsim los txo cov kev pheej hmoo ntawm kev tiv thaiv kab mob rau tib neeg lossis tib neeg cov tshuaj tiv thaiv kab mob.

Muab piv rau dev thiabnonhuman primates (NHPs)zoo li cynomolgus liab, kev siv cov npua me me hauv kev txhim kho cov tshuaj tsis muaj tshuaj kho tau raug txwv, feem ntau rau kev tshawb fawb tshuaj transdermal. Kev tshawb fawb thaum ntxov li xyoo 2010 tau qhia tias cov npua me me tuaj yeem hloov cov dev lossis NHPs hauv cov kev tshawb fawb tsis muaj tshuaj toxicology. Los ntawm 2014, lawv cov kev siv feem ntau txwv rau me me -molecule transdermal xa thiab kev soj ntsuam kev nyab xeeb ntawm lub plawv. Kev txwv tsis pub siv hauv biologics tuaj yeem raug ntaus nqi vim tsis muaj cov ntaub ntawv keeb kwm yav dhau los, cov tshuaj reagents, biomarkers, thiab kev siv tsawg hauv kev tshawb fawb txog kev loj hlob toxicity.

Txawm li cas los xij, kev tshawb fawb xyoo 2020 tau tshaj tawm tias 80% ntawm cov tuam txhab suav tias yog cov npua me me rau me me - molecule nonclinical kev soj ntsuam kev nyab xeeb, thiab ntau tus kuj tau soj ntsuam lawv siv hauv cov haujlwm biologics. Tus kab mob COVID-19 kis thoob qhov txhia chaw tau qhia txog cov teeb meem hauv NHP cov khoom siv thiab tus nqi, kom muaj kev txaus siab rau cov npua me me. Hauv xyoo 2022, FDA tau tshaj tawm cov lus qhia qhia lwm hom kab mob uas tsis yog kab mob rau kev tshawb fawb txog kev mob toxicology yog kev tshawb fawb ncaj ncees. Los ntawm tus tsiaj kev coj ncaj ncees, cov npua me me kuj yog qhov kev xaiv zoo tshaj NHPs.

Tam sim no Trends thiab Kev Tshawb Fawb Kev Lag Luam

Ib txoj kev tshawb fawb tsis ntev los no, luam tawm hauvLub Sijhawm thiab Kev Sib Tw rau Kev Siv Minipig hauv Kev Tsim Kho Tshuaj Tsis Kho Mob, tshawb fawb 21 lub tuam txhab los ntawm 2017-2022. Cov kev tshawb pom tau qhia tias nyob ib ncig ntawm 50% ntawm cov tuam txhab siv cov npua me me hauv cov kev tshawb fawb pharmacodynamic, thaum ntau dua 75% ua hauj lwm hauv PK thiab toxicology cov kev tshawb fawb-ib qho loj ntxiv piv rau cov kev tshawb fawb yav dhau los.

Cov npua me me feem ntau yog siv hauv me me - kev tshawb fawb molecule, ua raws li peptides thiab cov proteins me, thiab tsawg kawg hauv cov proteins loj lossis tshuaj tiv thaiv kab mob.

Cov teeb meem tseem ceeb nrog cov npua me me suav nrog:

• Test Article Yuav tsum muaj:Cov npua me me xav tau 60% ntau dua cov ntawv xeem tshaj li Beagle dev rau koob tshuaj -ntau qhov kev tshawb nrhiav thiab IND- ua kom muaj kev tshawb fawb, thiab txog li ob npaug rau ntev - cov kev tshawb fawb toxicology. Txawm li cas los xij, rau ntau qhov haujlwm, qhov no tsis txwv vim kev npaj kho mob txaus.

• Tsis muaj cov Reagents tshwj xeeb:Qhov tsis txaus ntawm cov tshuaj reagents rau kev tiv thaiv kab mob toxicity lossis molecular pathology kev tshawb fawb tuaj yeem ncua kev soj ntsuam, txawm hais tias cov tuam txhab tau tsim cov tshuaj reagents tailored rau me me npua.

• Cov ntaub ntawv keeb kwm tsis txaus:Cov ntaub ntawv keeb kwm kev tswj hwm rau cov npua me me yog qhov tsis tshua muaj siab dua li cov dev lossis cynomolgus liab. Txawm li cas los xij, kev siv cov npua me me yog maj mam txo qhov teeb meem no.

• Placental Transfer Challenges:Cov molecules loj feem ntau tsis hla cov placenta hauv cov npua me me, ua rau cov kev tshawb fawb txog kev ua me nyuam tsis zoo. Cov kev daws teeb meem muaj xws li kev tshawb fawb hauv genetic engineered nas lossis lwm txoj hauv kev molecular.

Qhov zoo

Txawm tias muaj kev sib tw, cov npua me me muaj ntau yam zoo:

• Physiological zoo sib xws:Lawv cov hlab plawv, metabolic, dermatological, thiab gastrointestinal systems zoo li cov tib neeg, ua rau lawv haum rau ntau yam tib neeg kev tshawb fawb kab mob.

• Kev txiav txim siab ncaj ncees:Cov npua me me yog qhov ua tau zoo dua qub piv rau NHPs.

• Practicality nyob rau hauv Juvenile Toxicology:Lawv qhov loj me me thiab kev sib deev sai (4-7 lub hlis) txo qhov kev thov rau cov tsiaj xeeb tub.

• Daim ntawv thov hauv Novel Therapies:Cov npua me me tau ua tiav zoo siv rau hauv tib neeg kev hloov pauv hauv nruab nrog cev, suav nrog kev mob plawv thiab daim tawv nqaij grafts.

Ntau qhov kev siv tau zoo ntawm cov npua me me hauv cov kev tshawb fawb noclinical qhia txog lawv cov kev siv ntau yam:

• Me -Molecule Drug rau Atherosclerosis:Tom qab cov dev Beagle pom adrenal cortical atrophy vim yog hom tsiaj- cov yam ntxwv tshwj xeeb, thiab cov cynomolgus liab ua tsis tau tiav qhov raug txaus, cov npua me me tau siv los ua cov hom tsis muaj nas, tau txais kev pom zoo los ntawm kev tswj hwm.

• Dual -Function Insulin/PCSK9 Inhibitor:Cov npua me me pom tau tias muaj kev zam zoo dua thiab raug ntau dua li cynomolgus liab, dhau los ua hom nyiam rau kev tshawb fawb toxicology.

• Recombinant Protein Therapy:Cov npua me me tau qhia txog kev ua tshuaj zoo sib xws rau tib neeg thiab nas, txhawb nqa lawv cov kev xaiv ua thawj hom tsis muaj nas txawm tias muaj kev soj ntsuam xyuas.

Xaus

Thaum cov npua me me muaj kev txwv, xws li cov ntawv xeem siab dua thiab cov ntaub ntawv keeb kwm tsawg, lawv lub cev zoo sib xws rau tib neeg thiab cov txiaj ntsig ua tau zoo ua rau lawv muaj txiaj ntsig zoo hauv kev tshawb fawb tsis muaj tshuaj. Tsim kom muaj kev tshawb fawb zoo tshaj plaws rau cov npua me me tuaj yeem tsim kom muaj kev sib tw kom zoo dua thiab ua rau txoj hauv kev rau kev coj mus siv dav dua yav tom ntej.