論文 - 阿部　洋

Synthesis of hydrophobic-tagged 2′-deoxy-modified cap analogs and its effect on mRNA translation

Zheyu Meng, Yuko Nakashima, Masahito Inagaki, Zhenmin Li, Susit Acharyya, Fumitaka Hashiya, Naoko Abe, Yasuaki Kimura, Hiroshi Abe

BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN   98 巻 ( 2 )   2025年2月

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OXFORD UNIV PRESS  

Messenger RNA (mRNA) has been implemented as COVID-19 vaccines. Following their success, the application of mRNA in cancer vaccines and protein replacement therapies is highly anticipated. The translational efficiency of mRNA largely depends on the cap structure located at its 5 ' end. In particular, the Cap-1 and Cap-2 structures are known to exhibit higher protein synthesis levels than the Cap-0 structure. Previously, we developed a method called the PureCap technique, which utilizes reversed-phase high-performance liquid chromatography (RP-HPLC) to purify highly capped mRNA with high precision, enabling accurate evaluation of translational activity. In this study, we synthesized cap analogs incorporating deoxyribose, and evaluated their mRNA synthesis efficiency and translational activity. Furthermore, by optimizing the transcription reaction conditions using the synthesized DNA-modified Cap series, we successfully improved the capping efficiency and mRNA yield. The deoxyadenosine-modified cap analog synthesized using the PureCap technique demonstrated 3.2-fold higher translational activity than the standard Cap-1 structure. Additionally, when using tetranucleotide cap analogs, consistent translational activity was observed, regardless of base sequence differences. This confirmed the general applicability of DNA-modified mRNA for translational activity.

DOI： 10.1093/bulcsj/uoaf006

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Internal cap-initiated translation for efficient protein production from circular mRNA

Fukuchi K., Nakashima Y., Abe N., Kimura S., Hashiya F., Shichino Y., Liu Y., Ogisu R., Sugiyama S., Kawaguchi D., Inagaki M., Meng Z., Kajihara S., Tada M., Uchida S., Li T.T., Maity R., Kawasaki T., Kimura Y., Iwasaki S., Abe H.

Nature Biotechnology     2025年2月

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Biotechnology  

Circular mRNA faces challenges in enhancing its translation potential as an RNA therapeutic. Here we introduce two molecular designs that bolster circular mRNA translation through an internal cap-initiated mechanism. The first consists of a circular mRNA with a covalently attached N7-methylguanosine (m7G) cap through a branching structure (cap-circ mRNA). This modification allows circular mRNA to recruit translation machinery and produce proteins more efficiently than internal ribosome entry site (IRES)-containing circular mRNAs. Combining with an N1-methylpseudouridine (m1Ψ) modification, cap-circ mRNA exhibits a lower acute immunostimulatory effect, maintaining high translation in mice. The second design features the non-covalent attachment of an m7G cap to a circular mRNA through hybridization with an m7G cap-containing oligonucleotide, enhancing translation by more than 50-fold. This setup allows circular mRNAs to synthesize reporter proteins upon hybridizing with capped mRNAs or long non-coding RNAs and to undergo rolling circle-type translation. These advancements broaden the therapeutic applications of circular mRNAs by minimizing their molecular size, elevating translation efficiency and facilitating cell-type-selective translation.

DOI： 10.1038/s41587-025-02561-8

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Covalently or non-covalently attached m<SUP>7</SUP>G cap enhances protein production from circular mRNA 招待有り 査読有り 国際誌

Hiroshi Abe, Naoko Abe

NATURE BIOTECHNOLOGY     2025年2月

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担当区分：筆頭著者,　最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PORTFOLIO  

DOI： 10.1038/s41587-025-02580-5

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Concise Affinity-Based Purification of Ligated mRNA for Structure-Activity Relationship Studies of Nucleosugar Modification Patterns 査読有り 国際誌

Yamada H., Iwai H., Hashiya F., Kimura Y., Abe H., Yamamoto J.

ChemBioChem   26 巻 ( 2 ) 頁： e202400711   2025年1月

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ChemBioChem  

Position-specific nucleoside sugar modifications have been shown to improve the translational activity and stability of chemically synthesized mRNA. For pharmaceutical applications of chemically modified mRNAs, a rapid purification methodology is imperative to identify the optimal modification pattern. However, while the chemical synthesis of mRNAs can be accomplished by splint ligation of oligonucleotide fragments, the current purification method for ligated mRNAs based on denaturing polyacrylamide gel electrophoresis tends to be time consuming. In this study, we developed a two-step affinity purification method for rapid sample preparation. In this method, ligated mRNA is captured by oligo dT magnetic beads and streptavidin magnetic beads with 3’-biotinylated oligo DNA, which are complementary to the 3’-poly(A) and 5’ terminal sequences of the target mRNA, respectively. Therefore, the target mRNA can be isolated from a complex mixture of splint ligations. Using this method, six sugar-modified mRNAs were simultaneously purified, and the translational activities of these mRNAs were evaluated immediately after purification. The results demonstrate that this methodology is suitable for the rapid preparation of various chemically synthesized mRNAs to identify their optimal modification patterns.

DOI： 10.1002/cbic.202400711

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Synthesis of Novel Cap Analogs Bearing Hydrophobic Purification Tag Toward Application for Preparation of Fully Capped Messenger RNA

Inagaki M., Abe H.

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry   83 巻 ( 1 ) 頁： 2 - 14   2025年1月

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出版者・発行元：Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry  

Messenger RNA (mRNA) is gaining attention as a new modality of oligonucleotide therapeutics. We have reported a new mRNA synthesis method, named the PureCap method, by in vitro transcription, which enables the production of completely capped mRNA. For this purpose, we designed and synthesized new cap analogs bearing hydrophobic o–nitrobenzyl groups, which function as purification tags for mRNA with a 5́–cap structure by reverse–phase high–performance liquid chromatography. In this paper, we describe the synthesis of new cap analogs, named PureCap analogs, and its application for completely capped mRNA synthesis.

DOI： 10.5059/yukigoseikyokaishi.83.2

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Synthesis of 2′-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs 査読有り 国際誌 Open Access

Nomura K., An S., Kobayashi Y., Kondo J., Shi T., Murase H., Nakamoto K., Kimura Y., Abe N., Ui-Tei K., Abe H.

Nucleic Acids Research   52 巻 ( 18 ) 頁： 10754 - 10774   2024年9月

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担当区分：最終著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nucleic Acids Research  

In this study, we report the synthesis of 2′-formamidonucleoside phosphoramidite derivatives and their incorporation into siRNA strands to reduce seed-based off-target effects of small interfering RNAs (siRNAs). Formamido derivatives of all four nucleosides (A, G, C and U) were synthesized in 5-11 steps from commercial compounds. Introducing these derivatives into double-stranded RNA slightly reduced its thermodynamic stability, but X-ray crystallography and CD spectrum analysis confirmed that the RNA maintained its natural A-form structure. Although the introduction of the 2′-formamidonucleoside derivative at the 2nd position in the guide strand of the siRNA led to a slight decrease in the on-target RNAi activity, the siRNAs with different sequences incorporating 2′-formamidonucleoside with four kinds of nucleobases into any position other than 2nd position in the seed region revealed a significant suppression of off-target activity while maintaining on-target RNAi activity. This indicates that 2′-formamidonucleosides represent a promising approach for mitigating off-target effects in siRNA therapeutics.

DOI： 10.1093/nar/gkae741

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2′-β-Methylselenyl nucleos(t)ide analogs as reverse transcriptase inhibitors against diverse HIV mutants 査読有り 国際誌 Open Access

Yoshida Y., Niimi Y., Fushihara D., Katakura H., Fukui R., Murase H., Tomoike F., Hashiya F., Murakami T., Kodama E.N., Suzuki T., Yasukawa K., Kimura Y., Abe H.

Bioorganic and Medicinal Chemistry   110 巻   頁： 117813 - 117813   2024年8月

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bioorganic and Medicinal Chemistry  

Nucleoside reverse transcriptase inhibitors (NRTIs) have been extensively studied as drugs targeting HIV RT. However, the practice or use of approved NRTIs lacking the 3ʹ-hydroxy group often promotes frequent HIV mutations and generates drug-resistance. Here, we describe a novel NRTI with 2′-β-methylselenyl modification. We found that this modification inhibited the DNA elongation reaction by HIV-1 RT despite having a 3′-hydroxy group. Moreover, the conformation of this nucleoside analog is controlled at C3′-endo, a conformation that resists excision from the elongating DNA by HIV RT. Accordingly, the designed analogs exhibited activity against both wild-type HIV and multidrug-resistant HIV mutants.

DOI： 10.1016/j.bmc.2024.117813

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Intracellular Delivery of Antisense Oligonucleotides by Tri-Branched Cyclic Disulfide Units 査読有り 国際誌 Open Access

Lyu F., Hakariya H., Hiraoka H., Li Z., Matsubara N., Soo Y., Hashiya F., Abe N., Shu Z., Nakamoto K., Kimura Y., Abe H.

ChemMedChem   19 巻 ( 20 ) 頁： e202400472   2024年7月

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ChemMedChem  

Therapeutic oligonucleotides, such as antisense DNA, show promise in treating previously untreatable diseases. However, their applications are still hindered by the poor membrane permeability of naked oligonucleotides. Therefore, it is necessary to develop efficient methods for intracellular oligonucleotide delivery. Previously, our group successfully developed disulfide-based Membrane Permeable Oligonucleotides (MPON), which achieved enhanced cellular uptake and gene silencing effects through an endocytosis-free uptake mechanism. Herein, we report a new molecular design for the next generation of MPON, called trimer MPON. The trimer MPON consists of a tri-branched backbone, three α-lipoic acid units, and a spacer linker between the oligonucleotides and tri-branched cyclic disulfide unit. We describe the design, synthesis, and functional evaluation of the trimer MPON, offering new insights into the molecular design for efficient oligonucleotide delivery.

DOI： 10.1002/cmdc.202400472

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Development and Comparison of 4-Thiouridine to Cytidine Base Conversion Reaction 招待有り 査読有り 国際誌 Open Access

Sana Ohashi, Mayu Nakamura, Susit Acharyya, Masahito Inagaki, Naoko Abe, Yasuaki Kimura, Fumitaka Hashiya, Hiroshi Abe

ACS Omegam   9 巻 ( 8 ) 頁： 9300 - 9308   2024年2月

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ACS Omega  

To study transcriptome dynamics without harming cells, it is essential to convert chemical bases. 4-Thiouridine (4sU) is a biocompatible uridine analogue that can be converted into a cytidine analogue. Although several reactions can convert 4sU into a cytidine analogue, few studies have compared the features of these reactions. In this study, we performed three reported base conversion reactions, including osmium tetroxide, iodoacetamide, and sodium periodate treatment, as well as a new reaction using 2,4-dinitrofluorobenzene. We compared the reaction time, conversion efficacy, and effects on reverse transcription. These reactions successfully converted 4sU into a cytidine analogue quantitatively using trinucleotides. However, the conversion efficacy and effect on reverse transcription vary depending on the reaction with the RNA transcript. OsO4 treatment followed by NH4Cl treatment showed the best base-conversion efficiency. Nevertheless, each reaction has its own advantages and disadvantages as a tool for studying the transcriptome. Therefore, it is crucial to select the appropriate reaction for the target of interest.

DOI： 10.1021/acsomega.3c08516

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Development of PCR primers enabling the design of flexible sticky ends for efficient concatenation of long DNA fragments 査読有り 国際誌 Open Access

Nomura K., Onda K., Murase H., Hashiya F., Ono Y., Terai G., Oka N., Asai K., Suzuki D., Takahashi N., Hiraoka H., Inagaki M., Kimura Y., Shimizu Y., Abe N., Abe H.

RSC Chemical Biology   5 巻 ( 4 ) 頁： 360 - 371   2024年2月

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：RSC Chemical Biology  

We developed chemically modified PCR primers that allow the design of flexible sticky ends by introducing a photo-cleavable group at the phosphate moiety. Nucleic acid derivatives containing o-nitrobenzyl photo-cleavable groups with a tert-butyl group at the benzyl position were stable during strong base treatment for oligonucleotide synthesis and thermal cycling in PCR reactions. PCR using primers incorporating these nucleic acid derivatives confirmed that chain extension reactions completely stopped at position 1 before and after the site of the photo-cleavable group was introduced. DNA fragments of 2 and 3 kbp, with sticky ends of 50 bases, were successfully concatenated with a high yield of 77%. A plasmid was constructed using this method. Finally, we applied this approach to construct a 48.5 kbp lambda phage DNA, which is difficult to achieve using restriction enzyme-based methods. After 7 days, we were able to confirm the generation of DNA of the desired length. Although the efficiency is yet to be improved, the chemically modified PCR primer offers potential to complement enzymatic methods and serve as a DNA concatenation technique.

DOI： 10.1039/d3cb00212h

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Topological capture of mRNA for silencing gene expression 査読有り 国際誌

Lyu F., Tomita T., Abe N., Hiraoka H., Hashiya F., Nakashima Y., Kajihara S., Tomoike F., Shu Z., Onizuka K., Kimura Y., Abe H.

Chemical Communications   59 巻 ( 77 ) 頁： 11564 - 11567   2023年9月

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Chemical Communications  

We describe herein topological mRNA capture using branched oligodeoxynucleotides (ODNs) with multiple reactive functional groups. These fragmented ODNs efficiently formed topological complexes on template mRNA in vitro. In cell-based experiments targeting AcGFP mRNA, the bifurcated reactive ODNs showed a much larger gene silencing effect than the corresponding natural antisense ODN.

DOI： 10.1039/d2cc06189a

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The Effect of γ Phosphate Modified Deoxynucleotide Substrates on PCR Activity and Fidelity 査読有り 国際誌 Open Access

Hashiya, F; Murase, H; Chandela, A; Hiraoka, H; Inagaki, M; Nakashima, Y; Abe, N; Nakamura, M; Terai, G; Kimura, Y; Ando, K; Oka, N; Asai, K; Abe, H

CHEMBIOCHEM   24 巻 ( 14 ) 頁： e202200572   2023年5月

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ChemBioChem  

Controlling PCR fidelity is an important issue for molecular biology and high-fidelity PCR is essential for gene cloning. In general, fidelity control is achieved by protein engineering of polymerases. In contrast, only a few studies have reported controlling fidelity using chemically modified nucleotide substrates. In this report, we synthesized nucleotide substrates possessing a modification on Pγ and evaluated the effect of this modification on PCR fidelity. One of the substrates, nucleotide tetraphosphate, caused a modest decrease in Taq DNA polymerase activity and the effect on PCR fidelity was dependent on the type of mutation. The use of deoxyadenosine tetraphosphate enhanced the A : T→G : C mutation dramatically, which is common when using Taq polymerase. Conversely, deoxyguanosine tetraphosphate (dG4P) suppressed this mutation but increased the G : C→A : T mutation during PCR. Using an excess amount of dG4P suppressed both mutations successfully and total fidelity was improved.

DOI： 10.1002/cbic.202200572

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Synthesis of nucleoside oligophosphates by electrophilic activation of phosphorothioate 査読有り 国際誌

Hasegawa, S; Inagaki, M; Kato, S; Li, ZM; Kimura, Y; Abe, H

ORGANIC & BIOMOLECULAR CHEMISTRY   21 巻 ( 19 ) 頁： 3997 - 4001   2023年5月

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Organic and Biomolecular Chemistry  

We herein report a new synthetic method for nucleoside oligophosphates based on electrophilic activation of 5′-phosphorothioate nucleotides. The treatment of phosphorothioate with 2,4-dinitrochlorobenzene (DNCB) efficiently afforded the key activated species, electrophilic thioester nucleotides (EPT-Ns), which were coupled with various phosphate reagents to afford the target nucleoside oligophosphates, including an mRNA cap analog.

DOI： 10.1039/d2ob02260e

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Cap analogs with a hydrophobic photocleavable tag enable facile purification of fully capped mRNA with various cap structures 査読有り 国際誌 Open Access

Inagaki, M; Abe, N; Li, ZM; Nakashima, Y; Acharyya, S; Ogawa, K; Kawaguchi, D; Hiraoka, H; Banno, A; Meng, ZY; Tada, M; Ishida, T; Lyu, P; Kokubo, K; Murase, H; Hashiya, F; Kimura, Y; Uchida, S; Abe, H

NATURE COMMUNICATIONS   14 巻 ( 1 ) 頁： 2657 - 2657   2023年5月

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Nature Communications  

Starting with the clinical application of two vaccines in 2020, mRNA therapeutics are currently being investigated for a variety of applications. Removing immunogenic uncapped mRNA from transcribed mRNA is critical in mRNA research and clinical applications. Commonly used capping methods provide maximum capping efficiency of around 80–90% for widely used Cap-0- and Cap-1-type mRNAs. However, uncapped and capped mRNA possesses almost identical physicochemical properties, posing challenges to their physical separation. In this work, we develop hydrophobic photocaged tag-modified cap analogs, which separate capped mRNA from uncapped mRNA by reversed-phase high-performance liquid chromatography. Subsequent photo-irradiation recovers footprint-free native capped mRNA. This approach provides 100% capping efficiency even in Cap-2-type mRNA with versatility applicable to 650 nt and 4,247 nt mRNA. We find that the Cap-2-type mRNA shows up to 3- to 4-fold higher translation activity in cultured cells and animals than the Cap-1-type mRNA prepared by the standard capping method.

DOI： 10.1038/s41467-023-38244-8

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Creation of single molecular conjugates of metal-organic cages and DNA 査読有り 国際誌 Open Access

Nakajo, T; Kusaka, S; Hiraoka, H; Nomura, K; Matsubara, N; Baba, R; Yoshida, Y; Nakamoto, K; Honma, M; Iguchi, H; Uchihashi, T; Abe, H; Matsuda, R

CHEMICAL COMMUNICATIONS   59 巻 ( 33 ) 頁： 4974 - 4977   2023年4月

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Chemical Communications  

Here we report the development of an equimolar conjugate of a metal-organic cage (MOC) and DNA (MOC-DNA). Several MOC-DNA conjugates were assembled into a programmed structure by coordinating with a template DNA having a complementary base sequence. Moreover, conjugation with the MOC drastically enhanced the permeability of DNA through the lipid bilayer, presenting great potential as a drug delivery system.

DOI： 10.1039/d3cc00460k

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Use of Iontophoresis Technology for Transdermal Delivery of a Minimal mRNA Vaccine as a Potential Melanoma Therapeutic 査読有り Open Access

Husseini, RA; Abe, N; Hara, T; Abe, H; Kogure, K

BIOLOGICAL & PHARMACEUTICAL BULLETIN   46 巻 ( 2 ) 頁： 301 - 308   2023年

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Biological and Pharmaceutical Bulletin  

mRNA vaccines have attracted considerable attention as a result of the 2019 coronavirus pandemic; however, challenges remain regarding use of mRNA vaccines, including insufficient delivery owing to the high molecular weights and high negative charges associated with mRNA. These characteristics of mRNA vaccines impair intracellular uptake and subsequent protein translation. In the current study, we prepared a minimal mRNA vaccine encoding a tumor associated antigen human gp10025-33 peptide (KVPRNQDWL), as a potential treatment for melanoma. Minimal mRNA vaccines have recently shown promise at improving the translational process, and can be prepared via a simple production method. Moreover, we previously reported the successful use of iontophoresis (IP) technology in the delivery of hydrophilic macromolecules into skin layers, as well as intracellular delivery of small interfering RNA (siRNA). We hypothesized that combining IP technology with a newly synthesized minimal mRNA vaccine can improve both transdermal and intracellular delivery of mRNA. Following IP-induced delivery of a mRNA vaccine, an immune response is elicited resulting in activation of skin resident immune cells. As expected, combining both technologies led to potent stimulation of the immune system, which was observed via potent tumor inhibition in mice bearing melanoma. Additionally, there was an elevation in mRNA expression levels of various cytokines, mainly interferon (IFN)-γ, as well as infiltration of cytotoxic CD8_ T cells in the tumor tissue, which are responsible for tumor clearance. This is the first report demonstrating the application of IP for delivery of a minimal mRNA vaccine as a potential melanoma therapeutic.

DOI： 10.1248/bpb.b22-00746

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Chemical synthesis of super messenger RNA medicine 査読有り

Tada Mizuki, Naoko Abe, Hiroshi Abe

Drug Delivery System   38 巻 ( 1 ) 頁： 15 - 23   2023年

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担当区分：最終著者,　責任著者  

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Chemical synthesis of super messenger RNA medicine 査読有り Open Access

Tada M., Abe N., Abe H.

Drug Delivery System   38 巻 ( 1 ) 頁： 15 - 23   2023年

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担当区分：最終著者,　責任著者   記述言語：日本語   掲載種別：研究論文（研究会，シンポジウム資料等）   出版者・発行元：Drug Delivery System  

Messenger RNA（mRNA）medicine was urgently approved in 2020 as a vaccine for COVID-19 . However, current mRNA therapeutics are not fully established, with challenges remaining in translation efficiency and drug delivery system. Therefore, further research is needed to adapt mRNA therapeutics to other diseases. Furthermore, the preparation of mRNA drugs is time-consuming and costly because of the biological methods used. Our laboratory has been working on chemical methods to solve these issues. In this paper, we introduce chemical modifications and novel capping reactions as a method to improve the translation efficiency of mRNA and the introduction of disulfide modification to oligonucleotide therapeutics as an effort on the drug delivery system.

DOI： 10.2745/dds.38.15

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mRNAの完全化学合成

小川 和哉, 阿部 洋

    2022年10月

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A 2′-modified uridine analog, 2'-<i>O</i>-(methylthiomethoxy)methyl uridine, for siRNA applications 査読有り 国際誌 Open Access

Lyu, F; An, S; Kobayashi, Y; Nomura, K; Baba, R; Abe, N; Hiraoka, H; Hashiya, F; Shu, ZM; Ui-Tei, K; Kimura, Y; Abe, H

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS   74 巻   頁： 128939 - 128939   2022年8月

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担当区分：最終著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bioorganic and Medicinal Chemistry Letters  

The medicinal applications of siRNAs have been intensively examined but are still hindered by their low molecular stability under biological conditions and off-target effects, etc. The introduction of chemical modifications to the nucleoside is a promising strategy for solving these limitations. Herein, we describe the development of a new uridine analog, U*, that has a (methylthiomethoxy)methoxy group at the 2′ position. The phosphoramidite reagent corresponding to U* was easily synthesized and the RNA oligonucleotides containing U* were stably prepared using a standard protocol for oligonucleotide synthesis. The introduction of U* into the siRNA resulted in positive or negative effects on the targeted gene silencing in a position-dependent manner, and the positive effects were attributed to the improved stability under biological conditions. The thermodynamic analysis of the U*-modified RNAs revealed a slight destabilization of the dsRNA, based depending on which U was strategically utilized to restrain the off-target effects of the siRNA. This study describes a rare example of nucleoside analogs with a large substitution at the 2′-position in the context of an siRNA application and is informative for the development of other analogs to further improve the molecular properties of siRNAs for medicinal applications.

DOI： 10.1016/j.bmcl.2022.128939

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