Implications of high-affinity hybridization by locked nucleic acid oligomers for inhibition of human telomerase

Anissa N. Elayadi, Dwaine A. Braasch, David R. Corey

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Oligonucleotides that contain locked nucleic acid (LNA) bases have remarkably high affinity for complementary RNA and DNA sequences. This increased affinity may facilitate the recognition of nucleic acid targets inside cells and thus improve our ability to use synthetic oligonucleotides for controlling cellular processes. Here we test the hypothesis that LNAs offer advantages for inhibiting human telomerase, a ribonucleoprotein that is critical for tumor cell proliferation. We observe that LNAs complementary to the telomerase RNA template are potent and selective inhibitors of human telomerase. LNAs can be introduced into cultured tumor cells using cationic lipid, with diffuse uptake throughout the cell. Transfected LNAs effectively inhibited intracellular telomerase activity up to 40 h post-transfection. Shorter LNAs of eight bases in length are also effective inhibitors of human telomerase. The melting temperatures of these LNAs for complementary sequences are superior to those of analogous peptide nucleic acid oligomers, emphasizing the value of LNA bases for high-affinity recognition. These results demonstrate that high-affinity binding by LNAs can be exploited for superior recognition of an intracellular target.

Original languageEnglish (US)
Pages (from-to)9973-9981
Number of pages9
JournalBiochemistry
Volume41
Issue number31
DOIs
StatePublished - Aug 6 2002

Fingerprint

Telomerase
Oligomers
Oligonucleotides
Tumors
Cultured Tumor Cells
Peptide Nucleic Acids
Complementary RNA
Ribonucleoproteins
DNA sequences
Cell proliferation
Nucleic Acids
Freezing
Transfection
Melting point
Complementary DNA
Cells
Cell Proliferation
Lipids
Temperature
locked nucleic acid

ASJC Scopus subject areas

  • Biochemistry

Cite this

Implications of high-affinity hybridization by locked nucleic acid oligomers for inhibition of human telomerase. / Elayadi, Anissa N.; Braasch, Dwaine A.; Corey, David R.

In: Biochemistry, Vol. 41, No. 31, 06.08.2002, p. 9973-9981.

Research output: Contribution to journalArticle

@article{9d2ed238c8bd4a97b4bb7c5b685644a0,
title = "Implications of high-affinity hybridization by locked nucleic acid oligomers for inhibition of human telomerase",
abstract = "Oligonucleotides that contain locked nucleic acid (LNA) bases have remarkably high affinity for complementary RNA and DNA sequences. This increased affinity may facilitate the recognition of nucleic acid targets inside cells and thus improve our ability to use synthetic oligonucleotides for controlling cellular processes. Here we test the hypothesis that LNAs offer advantages for inhibiting human telomerase, a ribonucleoprotein that is critical for tumor cell proliferation. We observe that LNAs complementary to the telomerase RNA template are potent and selective inhibitors of human telomerase. LNAs can be introduced into cultured tumor cells using cationic lipid, with diffuse uptake throughout the cell. Transfected LNAs effectively inhibited intracellular telomerase activity up to 40 h post-transfection. Shorter LNAs of eight bases in length are also effective inhibitors of human telomerase. The melting temperatures of these LNAs for complementary sequences are superior to those of analogous peptide nucleic acid oligomers, emphasizing the value of LNA bases for high-affinity recognition. These results demonstrate that high-affinity binding by LNAs can be exploited for superior recognition of an intracellular target.",
author = "Elayadi, {Anissa N.} and Braasch, {Dwaine A.} and Corey, {David R.}",
year = "2002",
month = "8",
day = "6",
doi = "10.1021/bi025907j",
language = "English (US)",
volume = "41",
pages = "9973--9981",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "31",

}

TY - JOUR

T1 - Implications of high-affinity hybridization by locked nucleic acid oligomers for inhibition of human telomerase

AU - Elayadi, Anissa N.

AU - Braasch, Dwaine A.

AU - Corey, David R.

PY - 2002/8/6

Y1 - 2002/8/6

N2 - Oligonucleotides that contain locked nucleic acid (LNA) bases have remarkably high affinity for complementary RNA and DNA sequences. This increased affinity may facilitate the recognition of nucleic acid targets inside cells and thus improve our ability to use synthetic oligonucleotides for controlling cellular processes. Here we test the hypothesis that LNAs offer advantages for inhibiting human telomerase, a ribonucleoprotein that is critical for tumor cell proliferation. We observe that LNAs complementary to the telomerase RNA template are potent and selective inhibitors of human telomerase. LNAs can be introduced into cultured tumor cells using cationic lipid, with diffuse uptake throughout the cell. Transfected LNAs effectively inhibited intracellular telomerase activity up to 40 h post-transfection. Shorter LNAs of eight bases in length are also effective inhibitors of human telomerase. The melting temperatures of these LNAs for complementary sequences are superior to those of analogous peptide nucleic acid oligomers, emphasizing the value of LNA bases for high-affinity recognition. These results demonstrate that high-affinity binding by LNAs can be exploited for superior recognition of an intracellular target.

AB - Oligonucleotides that contain locked nucleic acid (LNA) bases have remarkably high affinity for complementary RNA and DNA sequences. This increased affinity may facilitate the recognition of nucleic acid targets inside cells and thus improve our ability to use synthetic oligonucleotides for controlling cellular processes. Here we test the hypothesis that LNAs offer advantages for inhibiting human telomerase, a ribonucleoprotein that is critical for tumor cell proliferation. We observe that LNAs complementary to the telomerase RNA template are potent and selective inhibitors of human telomerase. LNAs can be introduced into cultured tumor cells using cationic lipid, with diffuse uptake throughout the cell. Transfected LNAs effectively inhibited intracellular telomerase activity up to 40 h post-transfection. Shorter LNAs of eight bases in length are also effective inhibitors of human telomerase. The melting temperatures of these LNAs for complementary sequences are superior to those of analogous peptide nucleic acid oligomers, emphasizing the value of LNA bases for high-affinity recognition. These results demonstrate that high-affinity binding by LNAs can be exploited for superior recognition of an intracellular target.

UR - http://www.scopus.com/inward/record.url?scp=0037031288&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037031288&partnerID=8YFLogxK

U2 - 10.1021/bi025907j

DO - 10.1021/bi025907j

M3 - Article

C2 - 12146961

AN - SCOPUS:0037031288

VL - 41

SP - 9973

EP - 9981

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 31

ER -