Binciken Sirna (Magungunan Kerna)

Keywords: Galnac - Sirna, Isarwar Sirna, Lysososomes Lysosomes, Tritosome, Lossoosome Catabolism, Losososomal Catabolism, Lysosomal Catpholism, Lysosomal Catphatase

Samfurin Iphayan

Shigowa da
RNA - Dangane da warkewa sun fito a matsayin hanyar canji a cikin magance cututtuka daban-daban ta hanyar yin shuru da aka yi niyya. Daga cikin wadannan jiyya, magungunan sirna suna samun kulawa ga ingancin ingancinsu da ingancin. Wani babban kalubale a isar da Sirna yana tabbatar da inganci mai ƙarfi Sirna ta tsere daga hanyar Endcytic Hanya kafin lalata da hanta a cikin hanta lysosomes da hepatocyte lysosomes A cikin binciken Vitro mai kara maida hankali kan yadda Sirna ke inganta sirna ta tsere yayin da aka yi hulɗa da kayan aikin salula. Wannan hulɗa ta ƙunshi abubuwa masu ƙima kamar Lysosome catabolism, Lysosomal Dalaci, da lalata ta hanyar lysosomalal acid phosphatal acid. Inganta waɗannan sigogi suna da mahimmanci don haɓaka isar da Sirna da cimma matsari na Sirna mai inganci.

Isar da Sirna da Lysosomal shiga
Inganci Sirna zuwa Hepatocytes sau da yawa dogaro da dilles kamar Lipid nanoparticles (LNPs) ko conjugates kamar Galnac - Sirna, wanda ya kai hanta. Duk da waɗannan sababbin sababbin abubuwa, ana fataucin Sirna da ke cikin hanta da hepatocyte Lysosomes, inda saurin Lysososome catabolism yana haifar da lalata. Yanayin acidic, wadatar da lysosomal acid, kalubalanci Lysosomal kwanciyar hankali da hana su tsere wa Sirna ta tsere. Don inganta sakamako na warkewa, bincike kan Sirna yana mai da hankali kan haɓaka Sirna ta tsere daga waɗannan ɗakunan Lysosomal, ta inganta isar da yankin yankin Sirna ta gaba.

Hanyar Galnac - Sirna Conjugates

Kasar Galmanac - Sirna Conjugate ta zama mai ban mamaki hanya don Sirna, Leverging The Halictory N - ACTECGLGACOCOAME (GANNAC) akan hepatocytes. Wannan hulɗa ta sauƙaƙe m endocytosis, ba da izinin Sirna ta shigar da sel sel yadda yakamata. Bayan Uguwa, da conjugates suna cikin gida mai kwakwalwa ta hanyar clthrin - Rage rna, wanda aka saki cikin lumen lumen (RNai) ta hanyar narkar da su Sialyl - Galnac na'urori.

Don haɓaka kwanciyar hankali da ingancin warkewa na Galnac - Sirna Conjugate, ana amfani da gyare-gyare da yawa.

• 2 '- f da 2' - ome gyara- Waɗannan gyare-gyare suna hana lalata rnase yayin riƙe kayan aikin RNA (RNai), suna kwaikwayon kayan aikin biophysical na halitta 2 '- OH rukuni.
• Gyare-gyare na phosphorothoate- Darajoji na Phosphorothiate a cikin 5 'da kuma 3' ƙarshen Sirna Strands yana ƙaruwa da ƙarfin aiki, kwanciyar hankali, da kuma rarenya.
• Ingantaccen Reni Triggers- The gama gari Sirna sun hada da samfuran nucleotide 21/21 tare da samfin nuchile 19 da 3/23 na nucleotide, wanda ke da matsayi na 5/23, wanda ke da matsayi na 5/23, wanda yake da ƙarshen ta 5/23 Wadannan ingantattun abubuwan ingantawa Sirna tasiri da tsawon rai.

Hukumar Lysosomal
Tafiyar Sirna daga Gudanarwa zuwa wurin aikinsa na aiwatarwa a hepatocytes da matsaloli, musamman ma sequatation da lalata. M catabolism na wulakanci a cikin wadannan bangarori, a cikin enzymes na enzey kamar lysosomal kwanciyar hankali da kuma iyaka yankin Sirna ku tsere. Shafar wadannan shinge na Lysosomal yana da matukar muhimmanci ga isar da Sirna mai nasara. Ci gaba a cikin - Mayar da hankali game da fasaha na Sirna a kan daidaito Catabolits na Lysosome don haɓaka yanayin walwala da kwanciyar hankali da hepatocyte lysosomes.

Katako Catabolism da Sirna wradation
A hepatocytes, catabolism na Lysosome catabolism shine babban katangar matsala ga kwanciyar hankali na warkewa. A tsakanin m acidieu na hanta lysosomes da hepatocyte lossoosomes lossoosomes, enzymatic comysphatal na acid phosphatase-hanzarta lalata sirna. Wannan lalacewar lalata ƙira mai lalacewa kuma yana rage taga don tasiri na Sirna ku tsere. Karatun kwanan nan akan Tsarin Sirna sun nuna cewa modulate Halin acid da kuma inganta amincin Sirna da haɓaka kayan aikin Sirna da ke inganta.

Yin amfani da samfuran tritosome a Binciken Sirna
Baya ga karatu na Lysosomes na al'ada, tritosomes na ware yana ba da ƙirar ci gaba don kimanta halaye na Lysosomal. Musamman, ber hepitosomes - wanda ke da linksomes na hepatic Lysosomes da aka ɗora da ba a yi tsinkayar Surfactants a cikin tsarin Catrabolism da kuma Membrane Dogon Lysosome. Wadannan nau'ikan samfuran da ke ba da damar masu bincike zasuyi mimik kuma suna amfani da hanyoyin lalata enzymatic. Ta hanyar haɗawa da fahimta daga sakandare na hawan hanta don inganta tserewa, ƙarshe yana ba da gudummawa ga mafi inganci RNA - Dangane da warkewa.

Tsarin bincike na rayuwa da zaɓi na Oligowides

Kamar yadda tare da kananan kwayoyin kwayoyin cuta, Sirna da ake kirkiro a cikin binciken ci gaba na Vitro na Vitro a lokacin da ci gaba na Panclacinical. Wadannan karatun ya kimanta tasirin catabolism na Lysosomal da rawar da lysphatalal acid a cikin lalata makein hanta lysosomes da hepatocyte lolsosomes. Ana sanya girmamawa kan inganta bayar da Sirna da tabbatar da fakiti Sirna ya tsere. Tsarin gwaji daban-daban - kamar hanta homogenates, ana ware hanta lysosomes, da kuma farko hepatocytes - ana aiki da su don kwaikwayon yanayin hepicatic. Inganta kwanciyar hankali da Lysosomal ta cikin waɗannan kimantawa shine mabuɗin don inganta aikin magungunan Sirna.

Ƙarshe

Sirna shapeutics suna canza magani ta hanyar ba da damar yin shuka da aka yi niyya, kodayake kalubalanci kamar lalacewar Lysosomal zauna. Actic Lysosomes da enzymes kamar su lysosomal acid hadar da tsarin kwanciyar hankali na Sirna (E.Gna, Phosphorothio) Inganta Tsaro da Lysosomal tserewa. A cikin binciken Vitro mai haɓaka tare da samfurin hanta yana haɓaka waɗannan ƙirar, suna tsara hanyar don ingantaccen tasiri RNA - Jawabin tushensu.