Efficacy of a Novel Class of RNA Interference Therapeutic Agents 英文参考文献.docVIP

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Efficacy of a Novel Class of RNA Interference Therapeutic Agents 英文参考文献.doc

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Efficacy of a Novel Class of RNA Interference Therapeutic Agents 英文参考文献

EfficacyofaNovelClassofRNAInterferenceTherapeutic Agents TomohiroHamasaki1.,HiroshiSuzuki1.,HisaoShirohzu1.,TakahiroMatsumoto1,2 , CorinaN.D’Alessandro-Gabazza2,3,PalomaGil-Bernabe2,DanielBoveda-Ruiz2,MasahiroNaito3, TetsuKobayashi3,MasaakiToda2,TakayukiMizutani1,5,OsamuTaguchi3,JohnMorser7,YutakaEguchi6, MasahikoKuroda5,TakahiroOchiya4,HirotakeHayashi1,EstebanC.Gabazza1,2*,TadaakiOhgi1* 1BONAC Corporation, BIO Factory 4F, Aikawa, Kurume, Fukuoka, Japan, 2Department of Immunology, Mie University Graduate School of Medicine, Mie, Japan, 3DepartmentofPulmonaryandCriticalCareMedicine,MieUniversityGraduateSchoolofMedicine,Mie,Japan,4NationalCancerCenterResearchInstitute,Tokyo,Japan, 5Department ofMolecularPathology,Tokyo Medical University, Tokyo, Japan, 6LaboratoryofMolecular Genetics, Department ofMedical Genetics,OsakaUniversity GraduateSchoolofMedicine,Osaka,Japan,7DivisionofHematology,StanfordUniversitySchoolofMedicine,Stanford,California,UnitedStatesofAmerica Abstract RNA interference (RNAi) is being widely used in functional gene research and is an important tool for drug discovery. However,canonicaldouble-strandedshortinterferingRNAsareunstableandinduceundesirableadverseeffects,andthus thereisnocurrentlyRNAi-basedtherapyintheclinic.WehavedevelopedanovelclassofRNAiagents,andevaluatedtheir effectivenessinvitroandinmousemodelsofacutelunginjury(ALI)andpulmonaryfibrosis.ThenovelclassofRNAiagents (nkRNAH,PnkRNATM)weresynthesizedonsolidphaseassingle-strandedRNAsthat,followingsynthesis,self-annealintoa unique helical structure containing a central stem and two loops. They are resistant to degradation and suppress their targetgenes.nkRNAandPnkRNAdirectedagainstTGF-b1mRNAameliorateoutcomesandinducenooff-targeteffectsin threeanimalmodelsoflungdisease.TheresultsofthisstudysupportthepathologicalrelevanceofTGF-b1inlungdiseases, andsuggestthepotentialusefulnessofthesenovelRNAiagentsfortherapeuticapplication. Citation: Hamasaki T, Suzuki H, Shirohzu H, Matsumoto T, D’Alessan