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E-book Antisense RNA Design, Delivery, and Analysis

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Penilaian

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Oligonucleotides are short single-stranded sections of DNA orRNA that contain 20-deoxyribo-nucleosides or ribo-nucleosides,respectively, which are linked by 30–50phosphodiester linkages(Fig.1a). Antisense oligonucleotides are those that are complemen-tary to a section of naturally occurring RNA, such as an mRNA or aviral RNA, to form Watson–Crick base pairs and to thus inhibit abiological function of that RNA. Zamecnik and Stephenson pio-neered this concept in 1978 by utilizing antisense oligodeoxyribo-nucleotides (ODNs) to bind and inhibit the replication of Roussarcoma virus (RSV) RNA [1]. This work followed much earlier(1969) studies of De Clercq et al. on interferon induction bysynthetic polynucleotides and their phosphorothioate analogues[2] and together these early studies heralded the new field ofnucleic acids therapeutics that began to accelerate in the mid tolate 1980s.Many further chemistry developments since then in the use ofsynthetic oligonucleotide analogues, as outlined below, as well asadvances in molecular biology, such as in the newer fields of short interfering RNA (siRNA) and non-coding RNAs, such as micro-RNA (miRNA), have led to the widespread and convenient use ofsynthetic oligonucleotides as antisense and siRNA reagents for geneablation or targeting of non-coding RNA, as well as their use inanimals and in humans leading to the approval of 12 drugs to date.In this chapter we outline the history of oligonucleotide chemistryin antisense and siRNA that has led to preclinical studies that haveguided their development with drug-like properties and henceclinical trials (Fig.2). We go on to discuss the development of theprinciples of widely used antisense gapmers and siRNAs as well astheir immune responses by triggering pattern recognition receptors(PRRs) and how such activities can be controlled or harnessed for. Early work in the 1960s and 1970s on phosphodiester and phos-photriester chemistry for the synthesis of ODNs required armies ofnucleic acids chemists for painstaking oligonucleotide synthesis insolution phase that took months to years for each synthesis (for example [4]). The revolution for molecular biologists came in thelate 1970s and early 1980s with the development of solid-phaseODN synthesis first suggested by Letsinger and Mahadevan in1965 [5] and later developed into working methods in the labora-tories of Gait [6–8] and Itakura [9]. These methods were thensuperseded by the more efficient phosphoramidite chemistry ofCaruthers and colleagues [10], which went on to be automated,such as by Applied Biosystems and other companies. The rapid andautomated synthesis allowed molecular biologists to obtain syn-thetic ODNs readily for biological purposes such as for sequencing,cloning, and gene synthesis. The history of oligonucleotide synthe-sis chemistry has been reviewed [11, 12]. Today standard andmodified ODNs can be obtained rapidly and efficiently on a smallto large scale through highly automated solid-phase DNA oligonu-cleotide synthesis for many biological and diagnostic purposes).

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Ketersediaan

Informasi Detail

Judul Seri

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No. Panggil

615.5 AAR a

Penerbit

New York : Springer Nature., 2022

Deskripsi Fisik

416 hlm

Bahasa

English

ISBN/ISSN

9781071620106

Klasifikasi

615.5

Tipe Isi

text

Tipe Media

computer

Tipe Pembawa

online resource

Edisi

-

Subjek

Therapeutics, Theraphy

Info Detail Spesifik

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Pernyataan Tanggungjawab

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Versi lain/terkait

Lampiran Berkas

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