Nucleic acid therapeutics: basic concepts and recent developments

Sharma, Vivek; Rungta, Pallavi; Prasad, Ashok K.

doi:10.1039/c3ra47841f

Cited by 80 publications

(60 citation statements)

References 200 publications

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“…PNAs from sequence-specific duplexes with mRNA inhibit its activity through steric inhibition of translation. Many further modifications exist that can be made to RNA molecules which are reviewed extensively in other publications [7,8].…”

Section: Third-generation Asosmentioning

confidence: 99%

“…These can be made shorter than other ASOs so reducing nonspecific protein binding. Most clinical ASOs fall into this category [7,8].…”

Section: Second-generation Asosmentioning

confidence: 99%

“…A number of approaches have been developed that include antisense deoxyribonucleic acid (DNA) oligonucleotides, small interfering RNAs (siRNAs) or microRNAs (miRNAs), and enzymes based either on DNA (DNAzymes) or RNA (RNAzymes) ( Table 1) [1,7,8].…”

Section: Antisense Oligonucleotidesmentioning

confidence: 99%

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Anti-sense oligonucleotide therapies for the treatment of hyperlipidaemia

Wierzbicki

Viljoen

2016

Expert Opinion on Biological Therapy

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Section: Third-generation Asosmentioning

confidence: 99%

“…These can be made shorter than other ASOs so reducing nonspecific protein binding. Most clinical ASOs fall into this category [7,8].…”

Section: Second-generation Asosmentioning

confidence: 99%

See 1 more Smart Citation

Anti-sense oligonucleotide therapies for the treatment of hyperlipidaemia

Wierzbicki

Viljoen

2016

Expert Opinion on Biological Therapy

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“…After the pioneering development in dideoxy-and acyclic-nucleos(t)ides [3], currently the most promising modification in the ribofuranose moiety has appeared through the inclusion of an extra methylene bridge between 2′-O & 4′-C atom and synthesis of oligonucleotides (ONs) involving the modified nucleosides, termed as locked nucleic acid (LNA) (Figure 1) [4,5]. Although, no significant potency was observed against cancer or viral infections by LNA monomers or its analogues [6]; there is hardly any synthetic oligonucleotide (ON) based therapeutic strategy which has not been allured by their unique features [4,5,7,8].…”

mentioning

confidence: 99%

“…These primarily include, (a) antigene approach to block transcription of a particular gene; (b) antisense approach to induce RNA degradation; (c) siRNA mediated RNA degradation; and (d) blocking of microRNA [7,8]. Since LNA possess high hybridization affinity and target selectivity, it is unsurprising that increasing success in cell-line based experiments has paved their way to five LNA-based modified ONs under active clinical trials ( Table 1).…”

mentioning

confidence: 99%

An astute synthesis of locked nucleic acid monomers

Sharma

Rungta

Maikhuri

et al. 2015

sustain chem process

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Novel attributes of Locked Nucleic Acid (LNA) makes it preferable over most of the other classes of modified nucleic acid analogues and therefore, it has been extensively explored in different synthetic oligonucleotide based therapeutics. In addition to five oligonucleotides of this class undergoing clinical trials, a healthy pipeline in pre-clinical studies validates the tenacity of LNA. Due to the increasing demand, an efficient biocatalytic methodology has recently been devised for the convergent synthesis of LNA monomers via selective enzymatic monoacetylation of diastereotopic hydroxymethyl functions of 3-O-benzyl-4-C-hydroxymethyl-1,2-O-isopropylidene-α-D-ribofuranose. This commentary article provides an insight into the different synthetic strategies followed for the synthesis of LNA monomers and their triumphs in clinical biotechnology.

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Neue Modalitäten für schwierige Zielstrukturen in der Wirkstoffentwicklung

et al. 2017

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Unsere sich stetig erweiternden Kenntnisse über biologische Systeme haben eine Vielzahl an hoch interessanten neuen biologischen Zielstrukturen aufgedeckt, deren Modulation möglicherweise neuartige Therapiemöglichkeiten für viele Krankheiten erschließt. Diese Angriffspunkte umfassen insbesondere Protein‐Protein‐ und Protein‐Nukleinsäure‐Wechselwirkungen, die jedoch durch klassische niedermolekulare Substanzen oftmals nicht adressierbar sind. Andere Substanzklassen oder Modalitäten werden daher benötigt, um diese Ziele anzuvisieren. Einige akademische Forschungsgruppen und pharmazeutische Unternehmen greifen daher zunehmend das Konzept der so genannten “neuen Modalitäten” auf. Dieser Aufsatz definiert erstmals diesen Begriff, der neuartige Peptidgerüststrukturen, Oligonukleotide, Hybride, molekulare Konjugate sowie auf neuartige Weise eingesetzte, klassische niedermolekulare Verbindungen berücksichtigt. Wir stellen die repräsentativsten Beispiele dieser Modalitäten vor, die auf große Bindungsoberflächen, wie sie in Protein‐Protein‐Wechselwirkungen vorkommen, sowie auf zentrale biologische Zellregulationsvorgänge abzielen.

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Nucleic acid therapeutics: basic concepts and recent developments

Cited by 80 publications

References 200 publications

Anti-sense oligonucleotide therapies for the treatment of hyperlipidaemia

Anti-sense oligonucleotide therapies for the treatment of hyperlipidaemia

An astute synthesis of locked nucleic acid monomers

Neue Modalitäten für schwierige Zielstrukturen in der Wirkstoffentwicklung

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