Lipid nanoparticles yog cov khoom me me ua los ntawm lipids, uas yog cov molecules uas tuaj yeem tsim cov kab mob lom. Lipid nanoparticles tuaj yeem siv los xa cov khoom siv caj ces, xws li DNA lossis RNA, mus rau hauv cov hlwb rau kev kho noob. Gene therapy yog ib txoj hauv kev los kho lossis tiv thaiv kab mob los ntawm kev hloov kho cov noob ntawm cov hlwb.
Vim li cas thiaj siv lipid nanoparticles rau kev kho noob?
Gene therapy muaj peev xwm kho tau ntau yam kab mob, xws li kab mob sib kis, mob qog noj ntshav thiab kab mob caj ces. Txawm li cas los xij, kev xa cov khoom siv caj ces mus rau hauv cov hlwb tsis yooj yim, vim tias nws tuaj yeem degraded los ntawm enzymes, tsis lees paub los ntawm lub cev tiv thaiv kab mob, los yog daig hauv cov endosomes (membrane- khi compartments hauv hlwb). Yog li ntawd, cov khoom siv caj ces yuav tsum tau tiv thaiv thiab thauj los ntawm kev xa khoom tuaj yeem kov yeej cov teeb meem no.
Lipid nanoparticles yog ib qho kev cog lus zoo tshaj plaws rau kev kho noob, vim tias lawv muaj ntau yam zoo:
Lawv tuaj yeem tiv thaiv cov khoom siv caj ces los ntawm kev puas tsuaj thiab kev tiv thaiv kab mob.
Lawv tuaj yeem fuse nrog cell membranes thiab tso cov khoom siv caj ces rau hauv cytoplasm.
Lawv tuaj yeem tsim los tsom rau cov hlwb lossis cov ntaub so ntswg los ntawm kev hloov kho lawv cov khoom nto.
Lawv tuaj yeem tsim tau yooj yim thiab ntsuas tau rau kev siv tshuaj kho mob.
Lawv muaj toxicity tsawg thiab immunogenicity piv rau cov kab mob kab mob, uas yog lwm txoj kev xa mus rau kev kho noob.
Lipid nanoparticles ua haujlwm li cas rau kev kho noob?
Lipid nanoparticles yog tsim los ntawm ntau hom lipids, xws li cationic lipids, pab lipids, fusogenic lipids thiab PEGylated lipids. Cationic lipids muaj cov nqi zoo uas tuaj yeem khi rau qhov tsis zoo ntawm cov khoom siv caj ces, tsim cov complex hu ua lipoplex. Pab lipids pab kom ruaj khov lipoplex thiab txhim kho nws cov khoom xa tuaj. Fusogenic lipids pab fuse cov lipid nanoparticle nrog cov cell membrane thiab tso cov khoom siv caj ces rau hauv cytoplasm. PEGylated lipids muaj polyethylene glycol (PEG) saw txuas rau lawv, uas tuaj yeem tiv thaiv lipid nanoparticle los ntawm lub cev tiv thaiv kab mob thiab ua kom nws lub sijhawm ncig hauv cov ntshav.
Lipid nanoparticles tuaj yeem tswj hwm los ntawm ntau txoj hauv kev, xws li kev txhaj tshuaj intravenous, intramuscular txhaj, nqus tau los yog siv tshuaj pleev. Thaum lawv ncav cuag lub hom phiaj, lawv cuam tshuam nrog cov cell membrane thiab xa cov khoom siv caj ces mus rau hauv lub cell. Cov khoom siv caj ces nkag mus rau hauv lub nucleus thiab hloov lossis kho cov noob tsis raug, lossis qhia txog kev kho cov protein.
Dab tsi yog qee qhov piv txwv ntawm lipid nanoparticles rau kev kho noob?
Lipid nanoparticles tau ua tiav siv los xa cov khoom sib txawv ntawm cov caj ces, xws li mRNA, siRNA, plasmid DNA thiab CRISPR-Cas9. Qee qhov piv txwv ntawm lipid nanoparticles rau kev kho noob yog:
Nyob rau hauv:Nov yog thawj zaug FDA- pom zoo lipid nanoparticle-raws li tshuaj rau kev kho cov kab mob transthyretin -mediated amyloidosis (hATTR), ib hom kab mob tsawg tsawg uas ua rau cov hlab ntsha puas thiab lub plawv tsis ua haujlwm. Onpattro xa cov siRNA uas ntsiag to mutant transthyretin (TTR) noob, txo qhov tsim ntawm TTR txawv txav uas tsim amyloid deposits nyob rau hauv cov ntaub so ntswg.
BNT162b2:Nov yog ib qho ntawm COVID-19 cov tshuaj tiv thaiv tsim los ntawm Pfizer thiab BioNTech, uas siv lipid nanoparticles xa mRNA uas encodes cov protein ntau ntawm SARS-CoV-2, tus kab mob uas ua rau COVID-19. mRNA qhia cov hlwb los tsim cov protein ntau, uas ua rau lub cev tsis muaj zog tiv thaiv kab mob.
CTX001:Qhov no yog ib qho kev sim noob caj noob ces- kho kho kho beta-thalassemia thiab mob qog nqaij hlav, uas yog cov kab mob hauv cov ntshav uas cuam tshuam rau kev tsim cov hemoglobin thiab kev ua haujlwm. CTX001 siv lipid nanoparticles xa CRISPR-Cas9, cov cuab yeej molecular uas tuaj yeem txiav thiab kho DNA. CRISPR-Cas9 lub hom phiaj thiab kho cov noob uas tswj cov fetal hemoglobin qhia, nce nws qib thiab txo cov tsos mob ntawm cov kab mob.
Dab tsi yog qee qhov nyuaj thiab cov lus qhia yav tom ntej rau lipid nanoparticles rau kev kho noob?
Lipid nanoparticles tau pom cov lus cog tseg zoo rau kev kho noob, tab sis lawv kuj ntsib qee qhov teeb meem thiab kev txwv, xws li:
Optimizing lawv qhov loj me, cov duab, nqi thiab muaj pes tsawg leeg kom ua tiav kev xa khoom zoo thiab qhov tshwj xeeb.
Tswj lawv cov biodistribution, pharmacokinetics thiab pharmacodynamics kom tsis txhob tawm ntawm -cov txiaj ntsig thiab toxicity.
Nkag siab txog lawv cov kev cuam tshuam nrog cov kua roj lom, cov hlwb thiab cov ntaub so ntswg kom txo qis kev tiv thaiv kab mob thiab cov kev mob tshwm sim.
Tsim cov qauv txheej txheem rau lawv cov yam ntxwv, kev tsim thiab kev tswj kom zoo kom ntseeg tau tias lawv muaj kev nyab xeeb thiab ua tau zoo.
Nthuav lawv daim ntawv thov dhau daim siab- tsom rau kev kho mob rau lwm yam kabmob thiab kab mob.
Txhawm rau kov yeej cov teeb meem no thiab ua ntej lipid nanoparticles rau kev kho noob, xav tau kev tshawb fawb ntxiv rau:
Tshawb nrhiav cov lipids tshiab thiab lipid-zoo li cov ntaub ntawv uas tuaj yeem txhim kho kev ruaj ntseg, kev ua haujlwm thiab biocompatibility ntawm lipid nanoparticles.
Tshawb xyuas cov txheej txheem thiab yam tseem ceeb uas cuam tshuam rau kev tsim, xa tawm thiab tso tawm ntawm lipid nanoparticles thiab lawv cov khoom lag luam genetic cargo.
Siv cov biomolecular corona ntawm lipid nanoparticles, uas yog txheej ntawm cov proteins thiab lwm yam molecules uas adsorb rau lawv nto hauv ib puag ncig lom neeg, los hloov lawv lub hom phiaj thiab kev ua haujlwm.
Tsim ntse thiab teb lipid nanoparticles uas tuaj yeem nkag siab thiab hloov mus rau qhov sib txawv stimuli, xws li pH, kub, enzymes lossis lub teeb.
Muab cov lipid nanoparticles nrog rau lwm cov thev naus laus zis, xws li nanomachine, biosensors lossis kev txawj ntse, los tsim cov txheej txheem tshiab thiab kho cov noob caj noob ces.
Lipid nanoparticles yog cov txheej txheem tshiab thiab ntau yam noob xa tuaj rau kev siv tshuaj kho mob. Los ntawm kev siv lawv lub peev xwm thiab daws lawv cov teeb meem, lipid nanoparticles tuaj yeem ua txoj hauv kev kom muaj txiaj ntsig zoo dua thiab kho tus kheej ntawm cov noob rau ntau yam kab mob.
