Sirna (Olilio Zvinodhaka) Kudzidza: Sirna Conjugates muLysosomal Kugadzikana uye Sirna Kutumira kwekukunda Sirna kupukunyuka Sirna

Mazwi akakosha: Galana, Sirna Dhivhiri, chirungu

Chigadzirwa chefae

Chigadzirwa Zita

Kutaurwa

Phase munhu chiropa chombo liversomes

250μl, 2mg / ml

Monkey Monkey Wechesosomes

250μl, 2mg / ml

Ifase imbwa chiropa liversomes

250μl, 2mg / ml

Iphase rat chiropa lysosomes

250μl, 2mg / ml

Iphae Mouse Provice Rysosomes

250μl, 2mg / ml

Iphase rat raizi tritosomes

250μl, 2mg / ml

Iphase Catabolic Buffer

A 1ML, B 10μL

Iphase Catabolic Buffer i

A 1ML, B 10μL

Iphase Catabolic Buffer II

1ml

Piafese munhu chiropa homogenize (ph 6.0)

10ML, 1: 4, W: v

Phase munhu chiropa chombo s9 chidimbu

0.5ml, 20mg / ml

Ifase Human Human Primary Hepatocytes

Mamiriyoni mashanu

Hipphae vanhu plasma

10ml

Hippake Human Tuya

1g

Nhanganyaya
RNA - Yakavakirwa maratidziro yakabuda senzira yekushandura maitiro mukurapa akasiyana zvirwere kuburikidza zvakanangwa gene kunyarara. Pakati peizvi kurapwa, mishonga yekuchiva iri kuwana hanya kune yavo yakagadziriswa chaiyo uye kushanda. Dambudziko rakakura muSirna kuburitsa Sirna Sirna kupukunyuka kubva kuThe Endocytic Pathay Pasati Pamberi Kusvibiswa muChiropa Lysososomes uye Hepatocyte Lysosomes. MuVitro zvidzidzo zvinowedzera kutarisa kuti Sirna mafomu anokurudzira Sirna kupukunyuka paunenge uchifambidzana nezvinhu zve cellular. Uku kudyidzana kunosanganisira zvinhu zvakashata senge lysosome catabolism, lysosomal kugadzikana, uye kusvibiswa naRsososomaal acid phazhat. Optimizing iyi parameter yakakosha kuti uwedzere kusimudzira Sirna kuendesa uye kuzadzisa Sirna Sirna kupukunyuka.

Sirna Dhirivhari uye Lysosomal Endrapment
Sirna Sirna kuburitsa kune Hepatocytes anowanzove anowanzove anotakura senge lipsid nanharticles (lnps) kana conjugates seGalnac - Sirna, iyo inotarisira chiropa - Pasinei nezvinhu izvi, chidimbu chakakosha cheSirna chinotengeswa kuChiropa Lysososomes uye Hepatocyte Lysosomes, uko nekukurumidza Rysosomes casabolism inotungamira mukusvibiswa. Nzvimbo yezviripo, yakafumiswa neLysosomal acid phazhatase, inonetsa Roshsosomal kugadzikana uye anotadzisa Sirna kupukunyuka. Kuti uvandudze zvinobuda, kutsvakisisa kweSirna kunotarisa pakukwirisa Sirna kupukunyuka kubva kune idzi lysosomal compartments, nekukasira kuvandudza zvakazara Sirna kutumira.

Mechanism yeGalnac - Sirna Conjugates

GALLAC - Sirna Conjugates nzira yekuvimbisa yeSirna yekutumira, iyo yakakwira mressity ye n - acetylgalactosamine (gacetlgalctáctosamine (gacetlg) ichisunga Uku kudyidzana kunofambisa nekukurumidza Endocytosis, kubvumira Sirna kuti apinde masero europa anobudirira. Pamusoro peanokwira, maconji ari mukati meClathrin - akabatanidzwa makomba, akaburitswa muCellular lumen

Kuti uwedzere kugadzikana uye kuratidzira Effices yeGallanac - Sirna Conjugates, Sirna Conjugates, akati wandei makemikari ekugadziridzwa anoshanda:

  • 2 '- F uye 2' - OME Shandiso- Izvi zvinoshandisirwa zvinodzivirira kurira kwernase uchiramba uchienderana ne rna kupindira
  • Phosphorooate modified- Kuwedzera phosphororioate mapoka kuma5 'uye 3' magumo eSirna tambo dzinowedzera potency, kugadzikana, uye rnai kusimba mu vivo.
  • Optimised rnai inokonzeresa- Zvakafanana Sirna magadzirirwo anosanganisira iyo 21/27 nucleotide template ne19 base vaviri vaviri uye 3 'vanopfuura, uye makumi maviri nenomwe. Aya azvino kutarisira anovandudza sirena kushanda uye hupenyu hurefu.

Lysosomal zvipingamupinyi
Rwendo rweSirna kubva kuUm yekutonga kune saiti yayo yekuita muHepatocytes ine zvipingamupinyi, kunyanya kutevedzana uye kusvibiswa mukati mechirozi manosoms uye hepatocyte lysosomes. Hartsive lysosome catabolism mune ino quarments, inotungamirirwa muchikamu ne enzymes seLysosomal acid phazhatase, inokanganisa Lysosomal kugadzikana uye inogumira sirna kupukunyuka. Kukurira idzi nyonganiso yekuzvimba ndeyekutsoropodzwa kweiyo yakabudirira Sirna kutumira. Kufambira mberi mu - Sirna tekinoroji inotarisa pane modulating lysolating lysosomal kusimudzira uye kusimudzira iyo yakawanda sirna yekupukunyuka

Lysosome Catabolism uye Sirna Degradation
Mune hepatocytes, lysome catabolism inhambadzi huru yekugadzikana kwekutonga kwekuratidzira sirna. Mukati meiyo acidic yemhando yechifananidzo uye hepatocyte lysosomes, zviitiko zveNzyematic-kusanganisira izvo zveLysososomal acid phosphating-inosimudzira Sirna kudzora. Uku kushatisa kunobatanidza Lysosomal kugadzikana uye kunoderedza hwindo kune inoshanda Sirna kupukunyuka. Recent fundo of Sirna mafomu airatidza kuti achimanikidza Lysosomal acid phosphating basa rinogona kuderedza rasha

Kushandisa mwero weTritoome muSirna research
Kuwedzera kune vanowanzoitika zvidzidzo zveRsosomal, tritosoms vari voga vanopa muenzaniso wepamberi kwekuongorora mansosomal maitiro. Kunyanya, rat chiropa tritosomes-ayo ari HEPTIC LYSOSOMES yakaremerwa neNON (IONIC SURFECATIONS - YAKABVUNZWA MUVITRO SYSE KUTI UCHIDZIDZE LYSOLISM Aya ma triposome models anogonesa vaongorori kuti vaongorore kutevedzera zvakanyanya uye kuwanda kweiyo enzymatic kusvibiswa maitiro ayo kukanganisa Sirna kugadzikana Sirna Stabiles Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna Sirna. Nekubatanidza nzwisiso kubva kuRat Revers Zvidzidzo, masayendisiti anogona kugadzirisa nzira dzekuumbwa kuti dzivise kupukunyuka Sirna

Metabolic kutsvagisa system uye kusarudzwa kweOligonucleides

Sezvineiwo neyechinyakare mishonga madhiragi mishonga, Sirna mafomu anoda kuteedzerwa muVitro metabolic kuutsa zvidzidzo panguva yekuvandudza preccliniki. Zvidzidzo izvi zvinoongorora kukanganisika kweiyo lysosome catabolism uye basa reLysosomal acid phazhating mune degrana mukati mechirozi manesosomes uye hepatocyte lysosomes. Kusimbisa kunoiswa pane optimizing Sirna kutumira uye kuona kuti sirna sirna kupukunyuka. Masisitimu akasiyana-siyana-akadai seiro chiropa homogenates, chiropa chombo liversomes, uye yekutanga hepatocytes-anoshandirwa kutevedzera nzvimbo yehupombwe. Kuvandudza Lysosomal kugadzikana kuburikidza nekuongororwa uku kiyi yekuvandudza mashandiro emishonga yesirna.

Bvunzo system

Mukana

Zvisina kunaka

Application

Chiropa s9

Ine yakawanda yeropa enzymes; zviri nyore kuwanikwa.

Yakaderera nucleise kutarisisa kupfuura muNative chiropa tishu.

Chidimbu chinotsiva chiropa tishu homogenates mune Sirna Dhizaina Zvidzidzo.

Chiropa homogenate

Pfuma mune zvinodhaka - metabolizing enzymes; yakakwira metabolic chiitiko.

Chiropa chevanhu chologenates zvine simba kuti uwane.

Yaishandiswa kuongorora Sirna Mhedzisiro pane lysosomal kugadzikana uye lysome catabolism.

Chiropa liversome

Yekutanga saiti ye metabolism; kupfuma mune hydrolytic enzymes.

Chaiyo subcellular chimiro chine midziyo yemisangano.

Kutsoropodza kuongorora Sirna kupukunyuka uye kukanganiswa kweRysosomal acid phosphatase.

Primary Hepatocyte

Zadzisa enzyme masisitimu; zvakakwirira zvemuviri senturance.

Mambres menduru inogona kukanganisa iyo inokwereta yevamwe - Sirna zvinodhaka.

Kuongororwa kweHepatic - Target Sirna Kutumira uye Sirna Kupukunyuka Kubudirira.

Chiropa microsomes

Zvemukati zvakakwirira zve cyp enzymes; Zvakanaka - Yakagadzwa System.

Lower nucleape chiitiko ichienzaniswa nenzvimbo dzeLysosomal.

Yakasarudzwa kubva pane metabolic mamiriro e sirna zvinodhaka.

Circulatory system yepakati (plasma / serum)

Mimics muVivo chiitiko chechirevo chechiitiko mukutenderera.

Anticoagulants anogona kukanganisa enzyme chiitiko.

Inowanzoshandiswa kuongorora kugadzikana kweSirna mune inotenderera system.

System nucleeee

Yakachena enzyme masisitimu nekukanganisa kushoma.

Haidzoreredze kuoma kwe mu vivo metabolism.

Kutanga kuongororwa kwemakemikari zvekugadziridzwa kwekuvandudza Sirna Dhizaina kugadzikana.

Target tissue matrix

Zvakananga zvinoenderana nekubudirira kwezvinodhaka mumatisiki.

Sampuli yemunhu matishu akaoma kuwana.

Kufungidzira maitiro e metabolic ye sirna zvinodhaka mune chinangwa tishu.

Mhedziso

Sirna kuronga kushandura mushonga wekunyatsoita nekuganhurira yakanangwa gene kunyarara, asi zvinonetsa senge kushatisa kweLysossomal kwakasara. Acisic lysosomes uye enzymes akadai saLysosomal acid phosphatase Hinder Sirna Stabiles, Sirna modifes MuVitro Ongororo ine mwero wechido kuti awedzere kuenderera mberi mafomu aya, achivhura nzira kuti adzorere rna inoshanda

 


Kutumira nguva: 2025 - 03 - 12 16:54:54
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