RNA therapeutics in the clinic

被引:54
作者
Curreri, Alexander [1 ,2 ]
Sankholkar, Disha [3 ]
Mitragotri, Samir [1 ,2 ]
Zhao, Zongmin [4 ,5 ]
机构
[1] Harvard Univ, John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[2] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02138 USA
[3] Lexington High Sch, Lexington, MA USA
[4] Univ Illinois, Coll Pharm, Dept Pharmaceut Sci, Chicago, IL 60612 USA
[5] Univ Illinois, Canc Ctr, Chicago, IL 60612 USA
关键词
antisense oligonucleotide; aptamer; clinical trial; gene therapy; lipid nanoparticle; mRNA; mRNA vaccine; RNA therapeutic; siRNA; FAMILIAL CHYLOMICRONEMIA SYNDROME; MOLECULAR-MECHANISMS; IN-VITRO; DELIVERY; VACCINES; HYPERCHOLESTEROLEMIA; OLIGONUCLEOTIDE; CHALLENGES; SIRNA; VACCINATION;
D O I
10.1002/btm2.10374
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Ribonucleic acid (RNA) therapeutics are being actively researched as a therapeutic modality in preclinical and clinical studies. They have become one of the most ubiquitously known and discussed therapeutics in recent years in part due to the ongoing coronavirus pandemic. Since the first approval in 1998, research on RNA therapeutics has progressed to discovering new therapeutic targets and delivery strategies to enhance their safety and efficacy. Here, we provide an overview of the current clinically relevant RNA therapeutics, mechanistic basis of their function, and strategies to improve their clinical use. We discuss the 17 approved RNA therapeutics and perform an in-depth analysis of the 222 ongoing clinical trials, with an emphasis on their respective mechanisms and disease areas. We also provide perspectives on the challenges for clinical translation of RNA therapeutics and suggest potential strategies to address these challenges.
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页数:19
相关论文
共 118 条
  • [71] Lipid Nanoparticles for Delivery of Therapeutic RNA Oligonucleotides
    Moss, Keith Henry
    Popova, Petya
    Hadrup, Sine R.
    Astakhova, Kira
    Taskova, Maria
    [J]. MOLECULAR PHARMACEUTICS, 2019, 16 (06) : 2265 - 2277
  • [72] 2021 FDA approvals
    Mullard, Asher
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2022, 21 (02) : 83 - 89
  • [73] Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds
    Nan, Yuchen
    Zhang, Yan-Jin
    [J]. FRONTIERS IN MICROBIOLOGY, 2018, 9
  • [74] Recent Progress in Aptamer Discoveries and Modifications for Therapeutic Applications
    Ni, Shuaijian
    Zhuo, Zhenjian
    Pan, Yufei
    Yu, Yuanyuan
    Li, Fangfei
    Liu, Jin
    Wang, Luyao
    Wu, Xiaoqiu
    Li, Dijie
    Wan, Youyang
    Zhang, Lihe
    Yang, Zhenjun
    Zhang, Bao-Ting
    Lu, Aiping
    Zhang, Ge
    [J]. ACS APPLIED MATERIALS & INTERFACES, 2021, 13 (08) : 9500 - 9519
  • [75] Novartis Pharmaceuticals, 2021, PHASE OPEN LABEL DOS
  • [76] Aptamers Chemistry: Chemical Modifications and Conjugation Strategies
    Odeh, Fadwa
    Nsairat, Hamdi
    Alshaer, Walhan
    Ismail, Mohammad A.
    Esawi, Ezaldeen
    Qaqish, Baraa
    Al Bawab, Abeer
    Ismail, Said I.
    [J]. MOLECULES, 2020, 25 (01):
  • [77] Omodamilola OI, 2018, J BIOMED PHARM SCI, V1, P115
  • [78] Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021
    Oster, Matthew E.
    Shay, David K.
    Su, John R.
    Gee, Julianne
    Creech, C. Buddy
    Broder, Karen R.
    Edwards, Kathryn
    Soslow, Jonathan H.
    Dendy, Jeffrey M.
    Schlaudecker, Elizabeth
    Lang, Sean M.
    Barnett, Elizabeth D.
    Ruberg, Frederick L.
    Smith, Michael J.
    Campbell, M. Jay
    Lopes, Renato D.
    Sperling, Laurence S.
    Baumblatt, Jane A.
    Thompson, Deborah L.
    Marquez, Paige L.
    Strid, Penelope
    Woo, Jared
    Pugsley, River
    Reagan-Steiner, Sarah
    DeStefano, Frank
    Shimabukuro, Tom T.
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2022, 327 (04): : 331 - 340
  • [79] Liposomal siRNA nanocarriers for cancer therapy
    Ozpolat, Bulent
    Sood, Anil K.
    Lopez-Berestein, Gabriel
    [J]. ADVANCED DRUG DELIVERY REVIEWS, 2014, 66 : 110 - 116
  • [80] mRNA vaccines - a new era in vaccinology
    Pardi, Norbert
    Hogan, Michael J.
    Porter, Frederick W.
    Weissman, Drew
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2018, 17 (04) : 261 - 279