Oligonucleotide Conjugates: Alteration of the Pharmacokinetic Properties of Antisense Agents

Manoharan, Muthiah; Tivel, Kathleen L.; Andrade, Laura K.; Mohan, V.; Condon, Thomas P.; Bennett, C. Frank; Cook, P. Dan

doi:10.1080/15257779508012513

Cited by 27 publications

(9 citation statements)

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“…12) [51]. Manoharan et al used PEG activated ester to attach PEG moieties with molecular weights 550, 2000 and 5000 to antisense ODN [54]. PEGs have also been attached to oligonucleotides by this approach.…”

Section: Conjugations Via Amide or Thiourea Linkagementioning

confidence: 99%

Chemical Strategies for Oligonucleotide-Conjugates Synthesis

Defrancq

Singh²,

Spinelli

2008

COC

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Oligonucleotide conjugates have found numerous applications in the field of diagnostics and therapeutics. Structurally diverse oligonucleotide conjugates have been prepared and evaluated for various applications. Research efforts have focused on the development of synthetic procedures to accomplish efficient oligonucleotide conjugation with different target molecules. Both on-support and solution-phase coupling procedures have been used to conjugate oligonucleotides. This review gives an account of major synthetic approaches available to prepare covalent oligonucleotide conjugates with diverse target molecules.

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Section: Conjugations Via Amide or Thiourea Linkagementioning

confidence: 99%

Chemical Strategies for Oligonucleotide-Conjugates Synthesis

Defrancq

Singh²,

Spinelli

2008

COC

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“…Several other types of backbone modifications have been tested, and like the above-mentioned modifications of the ribose, details of how these modifications are designed and how they function can be found in the articles cited. Briefly, modifications include oligonucleotide conjugates (49), methylphosphonate (29,56,63), phosphoramidate (23,34), morpholino (39,71), amide (28), peptide nucleic acids (PNA) (15,47), boranophosphate (66), methylene (methylimino) (MMI) (45), and 3Ј-methylene derivatives (7). Each type of modification has its specific applications, costs, and limitations.…”

Section: Chemical Compositionmentioning

confidence: 99%

Use of Antisense Oligonucleotides: Advantages, Controls, and Cardiovascular Tissue

2002

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Antisense oligonucleotides are short pieces of synthetic, chemically modified DNA or RNA that are designed to interact by Watson-Crick base pairing with mRNA encoding a targeted protein. During the past 20 years the technology associated with the development of antisense has improved dramatically, and emerging chemistries have made antisense oligonucleotides into powerful and versatile tools to study the function of proteins in living cells. The dramatic increase in novel genomic sequence information that has recently become available has generated enormous opportunities for the development of antisense oligonucleotides capable of altering the expression level of virtually any gene. With this will come a nearly equal opportunity to determine the role of individual proteins in a vast array of cardiovascular disease. The great specificity that these compounds exhibit in vitro suggests that they may also have an exciting future for development into therapeutics useful for the treatment of human disease. This review highlights some of the advances made in the field of antisense research, placing an emphasis on uses and proper controls.

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“…As a result, phosphorothioate oligos remain the most widely used base analogue, and are currently being tested in a number of clinical trials (Roth and Cristiano, 1997;Wagner and Flanagan, 1997). Second generation oligonucleotides include: substituting pyrimidines at the C-5 position with 5-methyl, 5-bromo and 5-propynyluracil (Lonnberg and Vuorio, 1996) replacement of the sugar and phosphate residues with alkylamide or carbamate linkage (Crooke and Bennett, 1996;Stirchak et al, 1989); 2 -O-propyl, 2 -methoxyethoxy, 2 -O-methyl, 2 -O-allyl and 2 -fluoro ribose modifications (Monia et al, 1993;Wagner, 1995;Crooke and Bennett, 1996); covalent linkage of functional groups, such as cholesterol, to alter physical properties, provide ligands or provide resistance (Krieg et al, 1993;Manoharan et al, 1995;Crooke and Bennett, 1996); replacement of the central phosphorus with a methylene group creating a formacetal linkage (Milligan et al, 1994). All of these modifications display either enhanced affinity or resistance or both, but many of them do not elicit RNase H activity.…”

Section: Antisense Technologymentioning

confidence: 99%

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et al. 1998

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Chemotherapy can cure a number of human cancers but resistance (either intrinsic or acquired) remains a significant problem in many patients and in many types of solid tumour. Combination chemotherapy (using drugs with different cellular targets/mechanisms) was introduced in order to kill cells which had developed resistance to a specific drug, and to allow delivery of a greater total dose of anti-cancer chemicals by combining drugs with different side-effects (Pratt et al., 1994). Nearly all anti-cancer drugs kill tumour cells by activating an endogenous bio-chemical pathway for cell suicide, known as programmed cell death or apoptosis.

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Oligonucleotide Conjugates: Alteration of the Pharmacokinetic Properties of Antisense Agents

Cited by 27 publications

References 0 publications

Chemical Strategies for Oligonucleotide-Conjugates Synthesis

Chemical Strategies for Oligonucleotide-Conjugates Synthesis

Use of Antisense Oligonucleotides: Advantages, Controls, and Cardiovascular Tissue

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