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rna therapeutics:updates and future potential

Science China(Life Sciences) 2023年第1期66卷 12-30页

作者： Caroline Zhang Biliang Zhang State Key Laboratory of Respiratory Disease Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China Guangzhou RiboBio Co. LtdGuangzhou 510663China Argorna Pharmaceuticals Co. Guangzhou 510530China

Recent advancements in the production,modification,and cellular delivery of rna molecules facilitated the expansion of rnabased therapeutics.The increasing understanding of rna biology initiated a corresponding growth in rna therapeutics.In this review,the general concepts of five classes of rna-based therapeutics,including rna interference-based therapies,antisense oligonucleotides,small activating rna therapies,circular rna therapies,and messenger rna-based therapeutics,will be discussed.Moreover,we also provide an overview of rna-based therapeutics that have already received regulatory approval or are currently being evaluated in clinical trials,along with challenges faced by these technologies.rna-based drugs demonstrated positive clinical trial results and have the ability to address previously“undruggable”targets,which delivers great promise as a disruptive therapeutic technology to fulfill its full clinical potentiality.

关键词： rna rna therapeutics mrna vaccine rnai

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A comprehensive analysis of the Bencao(herbal)small rna Atlas reveals novel rna therapeutics for treating human diseases

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Science China(Life Sciences) 2023年第10期66卷 2380-2398页

作者： Yinghao Cao Yexuan Lin Na Sun Xinyi Du Yixin Dong Song Mei Xingyu Deng Xiaobei Li Shaoting Guo Kegong Tang Jiaqi Liu Xiangyu Qiao Dandan Zhao Yuhao Qin Cong Zhang Tianyi Xin Xiaohu Shi Congzhao Zhou Tao Dong De-an Guo Benedikt MKessler Dong Xu Jingyuan Song Fengming Huang Xiaoyue Wang Chengyu Jiang State Key Laboratory of Common Mechanism Research for Major Diseases Department of BiochemistryInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Key Laboratory of Chinese Medicine Resources Conservation State Administration of Traditional Chinese Medicine of ChinaEngineering Research Center of Chinese Medicine Resource of Ministry of EducationInstitute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China Department of Traditional Chinese Medicine Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100005China Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences University of Science and Technology of ChinaHefei 230027China MRC Human Immunology Unit MRC Weatherall Institute of Molecular MedicineRadcliffe Department of MedicineUniversity of OxfordOxford OX37FZUK Chinese Academy of Medical Sciences(CAMS) CAMS Oxford Institute(COI)Nuffield Department of MedicineUniversity of OxfordOxfordOX37FZUK Shanghai Research Center for Modernization of Traditional Chinese Medicine National Engineering Laboratory for TCM Standardization TechnologyShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Target Discovery Institute Centre for Medicines DiscoveryNuffield Department of MedicineUniversity of OxfordOxfordOX37FZUK Department of Electrical Engineering and Computer Science and Christopher S.Bond Life Sciences CenterUniversity of MissouriColumbia MO 65211USA

Cross-kingdom herbal mi rna was first reported in 2012.Using a modified herbal extraction protocol,we obtained 73,677,287sequences by rna-seq from 245 traditional Chinese Medicine(TCM),of which 20,758,257 were unique sequences.We constructed a Bencao(herbal)small rna(s rna)Atlas(http://***),annotated the sequences by sequence-based clustering,and created a nomenclature system for Bencao s rnas.The profiles of 21,757 mi rnas in the Atlas were highly consistent with those of plant mi rnas in mi RBase.Using software tools,our results demonstrated that all human genes might be regulated by s rnas from the Bencao s rna Atlas,part of the predicted human target genes were experimentally validated,suggesting that Bencao s rnas might be one of the main bioactive components of herbal medicines.We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions.Moreover,the decoctosome,a lipo-nano particle consisting of 0.5%–2.5%of the decoction,demonstrated potent medical effects.We propose a Bencao(herbal)Index,including small-molecule compounds(SM),protein peptides(P),nucleic acid(N),non-nucleic and non-proteinogenic large-molecule compounds(LM)and elements from Mendeleev's periodic table(E),to quantitatively measure the medical effects of botanic medicine.The Bencao s rna Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine,and may provide potential remedies for the theory and practice of one medicine.

关键词： small rna herbal decoction cross-kingdom regulation traditional Chinese medicine rna oligonucleotide drug rna therapeutics Bencao small rna Atlas

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Small rnas:An expanding world with therapeutic promises

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Fundamental Research 2023年第5期3卷 676-682页

作者： Lan-Tao Gou Qifan Zhu Mo-Fang Liu State Key Laboratory of Molecular Biology Shanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China School of Life Science and Technology Shanghai Tech UniversityShanghai 201210China

Small non-coding rnas(sncrnas),such as micrornas(mirnas),small interfering rnas(sirnas),PIWIinteracting rnas(pirnas),and transfer rna(trna)-derived small rnas(tsrnas),play essential roles in regulating various cellular and developmental processes.Over the past three decades,researchers have identified novel sncrna species from various organisms.These molecules demonstrate dynamic expression and diverse functions,and they are subject to intricate regulation through rna modifications in both healthy and diseased states.Notably,certain sncrnas in gametes,particularly sperm,respond to environmental stimuli and facilitate epigenetic inheritance.Collectively,the in-depth understanding of sncrna functions and mechanisms has accelerated the development of small rna-based therapeutics.In this review,we present the recent advances in the field,including new sncrna species and the regulatory influences of rna modifications.We also discuss the current limitations and challenges associated with using small rnas as either biomarkers or therapeutic drugs.

关键词： Small non-coding rnas rna modifications Human diseases rna therapeutics Biomarkers

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