Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents
Identifieur interne : 002799 ( Main/Exploration ); précédent : 002798; suivant : 002800Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents
Auteurs : C. A. Stein [États-Unis] ; J. Bo Hansen [Danemark] ; Johnathan Lai [Danemark] ; Sijian Wu [États-Unis] ; Anatoliy Voskresenskiy [États-Unis] ; Anja H G [Danemark] ; Jesper Worm [Danemark] ; Maj Hedtj Rn [Danemark] ; Naira Souleimanian [États-Unis] ; Paul Miller [États-Unis] ; Harris S. Soifer [États-Unis] ; Daniella Castanotto [États-Unis] ; Luba Benimetskaya [États-Unis] ; Henrik Rum [Danemark] ; Troels Koch [Danemark]Source :
- Nucleic Acids Research [ 0305-1048 ] ; 2009.
Descripteurs français
- KwdFr :
- Animaux, Extinction de l'expression des gènes, Humains, Indicateurs et réactifs, Lignée cellulaire tumorale, Oligonucléotides (administration et posologie), Oligonucléotides (analyse), Oligonucléotides antisens (administration et posologie), Oligonucléotides antisens (analyse), Protéines proto-oncogènes c-bcl-2 (génétique), Protéines proto-oncogènes c-bcl-2 (métabolisme), Souris, Transfection.
- MESH :
- administration et posologie : Oligonucléotides, Oligonucléotides antisens.
- analyse : Oligonucléotides, Oligonucléotides antisens.
- génétique : Protéines proto-oncogènes c-bcl-2.
- métabolisme : Protéines proto-oncogènes c-bcl-2.
- Animaux, Extinction de l'expression des gènes, Humains, Indicateurs et réactifs, Lignée cellulaire tumorale, Souris, Transfection.
English descriptors
- KwdEn :
- Animals, Cell Line, Tumor, Gene Silencing, Humans, Indicators and Reagents, Mice, Oligonucleotides (administration & dosage), Oligonucleotides (analysis), Oligonucleotides, Antisense (administration & dosage), Oligonucleotides, Antisense (analysis), Proto-Oncogene Proteins c-bcl-2 (genetics), Proto-Oncogene Proteins c-bcl-2 (metabolism), Transfection.
- MESH :
- chemical , administration & dosage : Oligonucleotides, Oligonucleotides, Antisense.
- chemical , analysis : Oligonucleotides, Oligonucleotides, Antisense.
- chemical , genetics : Proto-Oncogene Proteins c-bcl-2.
- chemical , metabolism : Proto-Oncogene Proteins c-bcl-2.
- chemical : Indicators and Reagents.
- Animals, Cell Line, Tumor, Gene Silencing, Humans, Mice, Transfection.
Abstract
For the past 15–20 years, the intracellular delivery and silencing activity of oligodeoxynucleotides have been essentially completely dependent on the use of a delivery technology (e.g. lipofection). We have developed a method (called ‘gymnosis’) that does not require the use of any transfection reagent or any additives to serum whatsoever, but rather takes advantage of the normal growth properties of cells in tissue culture in order to promote productive oligonucleotide uptake. This robust method permits the sequence-specific silencing of multiple targets in a large number of cell types in tissue culture, both at the protein and mRNA level, at concentrations in the low micromolar range. Optimum results were obtained with locked nucleic acid (LNA) phosphorothioate gap-mers. By appropriate manipulation of oligonucleotide dosing, this silencing can be continuously maintained with little or no toxicity for >240 days. High levels of oligonucleotide in the cell nucleus are not a requirement for gene silencing, contrary to long accepted dogma. In addition, gymnotic delivery can efficiently deliver oligonucleotides to suspension cells that are known to be very difficult to transfect. Finally, the pattern of gene silencing of
Url:
DOI: 10.1093/nar/gkp841
PubMed: 19854938
PubMed Central: 2800216
Affiliations:
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Le document en format XML
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Soifer</name><affiliation wicri:level="2"><nlm:aff id="AFF1">City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Castanotto, Daniella" sort="Castanotto, Daniella" uniqKey="Castanotto D" first="Daniella" last="Castanotto">Daniella Castanotto</name><affiliation wicri:level="2"><nlm:aff id="AFF1">City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Benimetskaya, Luba" sort="Benimetskaya, Luba" uniqKey="Benimetskaya L" first="Luba" last="Benimetskaya">Luba Benimetskaya</name><affiliation wicri:level="2"><nlm:aff id="AFF1">Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467, USA,</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey=" Rum, Henrik" sort=" Rum, Henrik" uniqKey=" Rum H" first="Henrik" last=" Rum">Henrik Rum</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm, Denmark,</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm</wicri:regionArea><wicri:noRegion>Horsholm</wicri:noRegion></affiliation></author><author><name sortKey="Koch, Troels" sort="Koch, Troels" uniqKey="Koch T" first="Troels" last="Koch">Troels Koch</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm, Denmark,</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm</wicri:regionArea><wicri:noRegion>Horsholm</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19854938</idno><idno type="pmc">2800216</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800216</idno><idno type="RBID">PMC:2800216</idno><idno type="doi">10.1093/nar/gkp841</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000F46</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000F46</idno><idno type="wicri:Area/Pmc/Curation">000F46</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000F46</idno><idno type="wicri:Area/Pmc/Checkpoint">001378</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001378</idno><idno type="wicri:source">PubMed</idno><idno type="RBID">pubmed:19854938</idno><idno type="wicri:Area/PubMed/Corpus">001F87</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001F87</idno><idno type="wicri:Area/PubMed/Curation">001F87</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001F87</idno><idno type="wicri:Area/PubMed/Checkpoint">001E50</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001E50</idno><idno type="wicri:Area/Ncbi/Merge">000718</idno><idno type="wicri:Area/Ncbi/Curation">000718</idno><idno type="wicri:Area/Ncbi/Checkpoint">000718</idno><idno type="wicri:doubleKey">0305-1048:2009:Stein C:efficient:gene:silencing</idno><idno type="wicri:Area/Main/Merge">002825</idno><idno type="wicri:Area/Main/Curation">002799</idno><idno type="wicri:Area/Main/Exploration">002799</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Efficient gene silencing by delivery of locked nucleic acid antisense oligonucleotides, unassisted by transfection reagents</title><author><name sortKey="Stein, C A" sort="Stein, C A" uniqKey="Stein C" first="C. A." last="Stein">C. A. Stein</name><affiliation wicri:level="2"><nlm:aff id="AFF1">Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467, USA,</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Hansen, J Bo" sort="Hansen, J Bo" uniqKey="Hansen J" first="J. Bo" last="Hansen">J. Bo Hansen</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm, Denmark,</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm</wicri:regionArea><wicri:noRegion>Horsholm</wicri:noRegion></affiliation></author><author><name sortKey="Lai, Johnathan" sort="Lai, Johnathan" uniqKey="Lai J" first="Johnathan" last="Lai">Johnathan Lai</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm, Denmark,</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm</wicri:regionArea><wicri:noRegion>Horsholm</wicri:noRegion></affiliation></author><author><name sortKey="Wu, Sijian" sort="Wu, Sijian" uniqKey="Wu S" first="Sijian" last="Wu">Sijian Wu</name><affiliation wicri:level="2"><nlm:aff id="AFF1">Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467, USA,</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Voskresenskiy, Anatoliy" sort="Voskresenskiy, Anatoliy" uniqKey="Voskresenskiy A" first="Anatoliy" last="Voskresenskiy">Anatoliy Voskresenskiy</name><affiliation wicri:level="2"><nlm:aff id="AFF1">Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467, USA,</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="H G, Anja" sort="H G, Anja" uniqKey="H G A" first="Anja" last="H G">Anja H G</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm, Denmark,</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm</wicri:regionArea><wicri:noRegion>Horsholm</wicri:noRegion></affiliation></author><author><name sortKey="Worm, Jesper" sort="Worm, Jesper" uniqKey="Worm J" first="Jesper" last="Worm">Jesper Worm</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm, Denmark,</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm</wicri:regionArea><wicri:noRegion>Horsholm</wicri:noRegion></affiliation></author><author><name sortKey="Hedtj Rn, Maj" sort="Hedtj Rn, Maj" uniqKey="Hedtj Rn M" first="Maj" last="Hedtj Rn">Maj Hedtj Rn</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm, Denmark,</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm</wicri:regionArea><wicri:noRegion>Horsholm</wicri:noRegion></affiliation></author><author><name sortKey="Souleimanian, Naira" sort="Souleimanian, Naira" uniqKey="Souleimanian N" first="Naira" last="Souleimanian">Naira Souleimanian</name><affiliation wicri:level="2"><nlm:aff id="AFF1">Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467, USA,</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Miller, Paul" sort="Miller, Paul" uniqKey="Miller P" first="Paul" last="Miller">Paul Miller</name><affiliation wicri:level="2"><nlm:aff wicri:cut=" and" id="AFF1">Johns Hopkins School of Public Health, 615 N. Wolfe St., Baltimore, MD 21287</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>Johns Hopkins School of Public Health, 615 N. Wolfe St., Baltimore</wicri:cityArea></affiliation></author><author><name sortKey="Soifer, Harris S" sort="Soifer, Harris S" uniqKey="Soifer H" first="Harris S." last="Soifer">Harris S. Soifer</name><affiliation wicri:level="2"><nlm:aff id="AFF1">City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Castanotto, Daniella" sort="Castanotto, Daniella" uniqKey="Castanotto D" first="Daniella" last="Castanotto">Daniella Castanotto</name><affiliation wicri:level="2"><nlm:aff id="AFF1">City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010</wicri:regionArea><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Benimetskaya, Luba" sort="Benimetskaya, Luba" uniqKey="Benimetskaya L" first="Luba" last="Benimetskaya">Luba Benimetskaya</name><affiliation wicri:level="2"><nlm:aff id="AFF1">Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467, USA,</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Albert Einstein-Montefiore Cancer Center, Montefiore Medical Center, 111 E. 210 St., Bronx, NY 10467</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey=" Rum, Henrik" sort=" Rum, Henrik" uniqKey=" Rum H" first="Henrik" last=" Rum">Henrik Rum</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm, Denmark,</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm</wicri:regionArea><wicri:noRegion>Horsholm</wicri:noRegion></affiliation></author><author><name sortKey="Koch, Troels" sort="Koch, Troels" uniqKey="Koch T" first="Troels" last="Koch">Troels Koch</name><affiliation wicri:level="1"><nlm:aff id="AFF1">Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm, Denmark,</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Santaris Pharma A/C, Kogle Alle 6, DK-2970, Horsholm</wicri:regionArea><wicri:noRegion>Horsholm</wicri:noRegion></affiliation></author></analytic><series><title level="j">Nucleic Acids Research</title><idno type="ISSN">0305-1048</idno><idno type="eISSN">1362-4962</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Gene Silencing</term><term>Humans</term><term>Indicators and Reagents</term><term>Mice</term><term>Oligonucleotides (administration & dosage)</term><term>Oligonucleotides (analysis)</term><term>Oligonucleotides, Antisense (administration & dosage)</term><term>Oligonucleotides, Antisense (analysis)</term><term>Proto-Oncogene Proteins c-bcl-2 (genetics)</term><term>Proto-Oncogene Proteins c-bcl-2 (metabolism)</term><term>Transfection</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Extinction de l'expression des gènes</term><term>Humains</term><term>Indicateurs et réactifs</term><term>Lignée cellulaire tumorale</term><term>Oligonucléotides (administration et posologie)</term><term>Oligonucléotides (analyse)</term><term>Oligonucléotides antisens (administration et posologie)</term><term>Oligonucléotides antisens (analyse)</term><term>Protéines proto-oncogènes c-bcl-2 (génétique)</term><term>Protéines proto-oncogènes c-bcl-2 (métabolisme)</term><term>Souris</term><term>Transfection</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Oligonucleotides</term><term>Oligonucleotides, Antisense</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analysis" xml:lang="en"><term>Oligonucleotides</term><term>Oligonucleotides, Antisense</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Proto-Oncogene Proteins c-bcl-2</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Proto-Oncogene Proteins c-bcl-2</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Indicators and Reagents</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Oligonucléotides</term><term>Oligonucléotides antisens</term></keywords><keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Oligonucléotides</term><term>Oligonucléotides antisens</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Protéines proto-oncogènes c-bcl-2</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Protéines proto-oncogènes c-bcl-2</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line, Tumor</term><term>Gene Silencing</term><term>Humans</term><term>Mice</term><term>Transfection</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Extinction de l'expression des gènes</term><term>Humains</term><term>Indicateurs et réactifs</term><term>Lignée cellulaire tumorale</term><term>Souris</term><term>Transfection</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>For the past 15–20 years, the intracellular delivery and silencing activity of oligodeoxynucleotides have been essentially completely dependent on the use of a delivery technology (e.g. lipofection). We have developed a method (called ‘gymnosis’) that does not require the use of any transfection reagent or any additives to serum whatsoever, but rather takes advantage of the normal growth properties of cells in tissue culture in order to promote productive oligonucleotide uptake. This robust method permits the sequence-specific silencing of multiple targets in a large number of cell types in tissue culture, both at the protein and mRNA level, at concentrations in the low micromolar range. Optimum results were obtained with locked nucleic acid (LNA) phosphorothioate gap-mers. By appropriate manipulation of oligonucleotide dosing, this silencing can be continuously maintained with little or no toxicity for >240 days. High levels of oligonucleotide in the cell nucleus are not a requirement for gene silencing, contrary to long accepted dogma. In addition, gymnotic delivery can efficiently deliver oligonucleotides to suspension cells that are known to be very difficult to transfect. Finally, the pattern of gene silencing of <italic>in vitro</italic> gymnotically delivered oligonucleotides correlates particularly well with <italic>in vivo</italic> silencing. The establishment of this link is of particular significance to those in the academic research and drug discovery and development communities.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Akhtar, S" uniqKey="Akhtar S">S Akhtar</name></author><author><name sortKey="Basu, S" uniqKey="Basu S">S Basu</name></author><author><name sortKey="Wickstrom, W" uniqKey="Wickstrom W">W Wickstrom</name></author><author><name sortKey="Juliano, R" uniqKey="Juliano R">R Juliano</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walder, R" uniqKey="Walder R">R Walder</name></author><author><name sortKey="Walder, J" uniqKey="Walder J">J Walder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marcusson, E" uniqKey="Marcusson E">E Marcusson</name></author><author><name sortKey="Bhat, B" uniqKey="Bhat B">B Bhat</name></author><author><name sortKey="Manoharan, M" uniqKey="Manoharan 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sort="Stein, C A" uniqKey="Stein C" first="C. A." last="Stein">C. A. Stein</name></region><name sortKey="Benimetskaya, Luba" sort="Benimetskaya, Luba" uniqKey="Benimetskaya L" first="Luba" last="Benimetskaya">Luba Benimetskaya</name><name sortKey="Castanotto, Daniella" sort="Castanotto, Daniella" uniqKey="Castanotto D" first="Daniella" last="Castanotto">Daniella Castanotto</name><name sortKey="Miller, Paul" sort="Miller, Paul" uniqKey="Miller P" first="Paul" last="Miller">Paul Miller</name><name sortKey="Soifer, Harris S" sort="Soifer, Harris S" uniqKey="Soifer H" first="Harris S." last="Soifer">Harris S. Soifer</name><name sortKey="Souleimanian, Naira" sort="Souleimanian, Naira" uniqKey="Souleimanian N" first="Naira" last="Souleimanian">Naira Souleimanian</name><name sortKey="Voskresenskiy, Anatoliy" sort="Voskresenskiy, Anatoliy" uniqKey="Voskresenskiy A" first="Anatoliy" last="Voskresenskiy">Anatoliy Voskresenskiy</name><name sortKey="Wu, Sijian" sort="Wu, Sijian" uniqKey="Wu S" first="Sijian" last="Wu">Sijian Wu</name></country><country name="Danemark"><noRegion><name sortKey="Hansen, J Bo" sort="Hansen, J Bo" uniqKey="Hansen J" first="J. Bo" last="Hansen">J. Bo Hansen</name></noRegion><name sortKey=" Rum, Henrik" sort=" Rum, Henrik" uniqKey=" Rum H" first="Henrik" last=" Rum">Henrik Rum</name><name sortKey="H G, Anja" sort="H G, Anja" uniqKey="H G A" first="Anja" last="H G">Anja H G</name><name sortKey="Hedtj Rn, Maj" sort="Hedtj Rn, Maj" uniqKey="Hedtj Rn M" first="Maj" last="Hedtj Rn">Maj Hedtj Rn</name><name sortKey="Koch, Troels" sort="Koch, Troels" uniqKey="Koch T" first="Troels" last="Koch">Troels Koch</name><name sortKey="Lai, Johnathan" sort="Lai, Johnathan" uniqKey="Lai J" first="Johnathan" last="Lai">Johnathan Lai</name><name sortKey="Worm, Jesper" sort="Worm, Jesper" uniqKey="Worm J" first="Jesper" last="Worm">Jesper Worm</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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