Gapped oligomers having site specific chiral phosphorothioate internucleoside linkages
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07H-021/04
C07H-021/00
출원번호
US-0438989
(1999-11-12)
발명자
/ 주소
Sanghvi, Yogesh S.
Manoharan, Muthiah
출원인 / 주소
ISIS Pharmaceuticals, Inc.
대리인 / 주소
ISIS Patent Department
인용정보
피인용 횟수 :
111인용 특허 :
144
초록
Novel chiral compounds that mimic and/or modulate the activity of wild-type nucleic acids are disclosed. In general, the compounds are phosphorothioate oligonucleotides wherein the 5′, and the 3′-terminal internucleoside linkages are chirally Sp and internal internucleoside linkages are chirally Rp.
대표청구항▼
1. An oligomeric compound of the formula:5′-(Nu1?L1)n?Y?(L2-Nu2)p?3′wherein:each Nu1 and Nu2, independently, has the formula: whereinBx is a heterocyclic base moiety; Lx is hydrogen, a protecting group or a substituent group; one of R12, R13 and R14 is hydroxyl, a protected hydroxyl, a covalent atta
1. An oligomeric compound of the formula:5′-(Nu1?L1)n?Y?(L2-Nu2)p?3′wherein:each Nu1 and Nu2, independently, has the formula: whereinBx is a heterocyclic base moiety; Lx is hydrogen, a protecting group or a substituent group; one of R12, R13 and R14 is hydroxyl, a protected hydroxyl, a covalent attachment to a solid support, a nucleoside, an oligonucleoside, a nucleotide, an oligonucleotide, a conjugate group or an optionally protected substituent group; another of R12, R13 and R14 is hydrogen, hydroxyl, a protected hydroxyl or an optionally protected substituent group; the remaining of R12, R13 and R14, of Nu1, is L1; the remaining of R12, R13 and R14, of Nu2, is L2; each L1 and each L2 is, independently, a phosphodiester, phosphorodithioate; chiral Sp phosphorothioate; phosphoramidate; thiophosphoramidate; phosphonate; methylene phosphonate; phosphotriesters; thionoalkylphosphonate; thionoalkylphosphotriester; boranophosphate; boranothiophosphate; thiodiester; thionocarbamate; siloxane; carbamate; sulfamate; morpholino sulfamide; sulfonamide; sulfide; sulfonate; N,N′-dimethylhvdrazine; thioformacetal; formacetal; thioketal; ketal; amine (?NH?CH2?CH2?); hydroxylamine; hydroxylimine; hydrazinyl; amide (?CH2?N(JJ)?C(O)?) and (?CH2?C(O)?N(JJ)?); oxime (?CH2?O?N?CH?); or alkylphosphorus (?C(JJ)2?P(?O)(OJJ)?C(JJ)2?C(JJ)2?) internucleoside linkage, wherein each JJ is, independently, hydrogen or C1 to C10 alkyl wherein at least one of L1 and L2 is other than phosphodiester; Y has the formula: wherein;each Rp is a chiral Rp phosphorothioate internucleotide linkage; and each n, m and p is, independently, from 1 to 100; where the sum of n, m and p is from 3 to about 200; wherein the oligomeric compound comprises from 5 to about 50 nucleosides. 2. The oligomeric compound of claim 1 wherein at least one Nu1 or at least one Nu2 comprises a substituent group.3. The oligomeric compound of claim 2 wherein at least one Nu1 and at least one Nu2 independently comprise a substituent group.4. The oligomeric compound of claim 1 wherein each Nu1 and each Nu2 independently comprises a substituent group.5. The oligomeric compound of claim 2 wherein said substituent group is covalently attached to the 2′, 3′ or 5′-position of said Nu1 or Nu2.6. The oligomeric compound of claim 5 wherein said substituent group is covalently attached to the 2′-position of said Nu1 or Nu2.7. The oligomeric compound of claim 1 wherein each of said substituent groups is, independently, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, C5-C20 aryl, O-alkyl, O-alkenyl, O-alkynyl, O-alkylamino, O-alkylalkoxy, O-alkylaminoalkyl, O-alkyl imidazole, thiol, S-alkyl, S-alkenyl, S-alkynyl, NH-alkyl, NH-alkenyl, NH-alkynyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, N-phthalimido, halogen keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, heterocycle, carbocycle, polyamine, polyamide, polyalkylene glycol, and polyether;or each substituent group has one of formula I or II: wherein:Z0 is O, S or NH; J is a single bond, O or C(?O); E is C1-C10 alkyl, N(R1)(R2), N(R1)(R5), N?C(R1)(R2), N?C(R1)(R5) or has one of formula III or IV; each R6, R7, R8, R9 and R10 is, independently, hydrogen, C(O)R11, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, alkylsulfonyl, arylsulfonyl, a chemical functional group or a conjugate group, wherein the substituent groups are selected from hydroxyl, amino, alkoxy, carboxy, benzyl, phenyl, nitro, thiol, thioalkoxy, halogen, alkyl, aryl, alkenyl and alkynyl; or optionally, R7 and R8, together form a phthalimido moiety with the nitrogen atom to which they are attached; or optionally, R9 and R10, together form a phthalimido moiety with the nitrogen atom to which they are attached; each R11 is, independently, substituted or unsubstituted C1-C10 alkyl, trifluoromethyl, cyanoethyloxy, methoxy, ethoxy, t-butoxy, allyloxy, 9-fluorenylmethoxy, 2-(trimethylsilyl)ethoxy, 2,2,2-trichloroethoxy, benzyloxy, butyryl, iso-butyryl, phenyl or aryl; R5 is T-L, T is a bond or a linking moiety; L is a chemical functional group, a conjugate group or a solid support material; each R1 and R2 is, independently, H, a nitrogen protecting group, substituted or unsubstituted C1-C10 alkyl, substituted or unsubstituted C2-C10 alkenyl, substituted or unsubstituted C2-C10 alkynyl, wherein said substitution is OR3, SR3, NH3+, N(R3)(R4), guanidino or acyl where said acyl is an acid amide or an ester; or R1 and R2, together, are a nitrogen protecting group or are joined in a ring structure that optionally includes an additional heteroatom selected from N and O; or R1, T and L, together, are a chemical functional group; each R3 and R4 is, independently, H, C1-C10 alkyl, a nitrogen protecting group, or R3 and R4, together, are a nitrogen protecting group; or R3 and R4 are joined in a ring structure that optionally includes an additional heteroatom selected from N and O; Z4 is OX, SX, or N(X)2; each X is, independently, H, C1-C8 alkyl, C1-C8 haloalkyl, C(?NH)N(H)R5, C(?O)N(H)R5 or OC(?O)N(H)R5; R5 is H or C1-C8 alkyl; Z1, Z2 and Z3 comprise a ring system having from about 4 to about 7 carbon atoms or having from about 3 to about 6 carbon atoms and 1 or 2 hetero atoms wherein said hetero atoms are selected from oxygen, nitrogen and sulfur and wherein said ring system is aliphatic, unsaturated aliphatic, aromatic, or saturated or unsaturated heterocyclic; Z5 is alkyl or haloalkyl having 1 to about 10 carbon atoms, alkenyl having 2 to about 10 carbon atoms, alkynyl having 2 to about 10 carbon atoms, aryl having 6 to about 14 carbon atoms, N(R1)(R2) OR1, halo, SR1 or CN; each q1 is, independently, an integer from 1 to 10; each q2 is, independently, 0 or 1; q3 is 0 or an integer from 1 to 10; q4 is an integer from 1 to 10; q5 is from 0, 1 or 2; and provided that when q3 is 0, q4 is greater than 1.8. The oligomeric compound of claim 1 wherein at least one R14 is L1 or L2.9. The oligomeric compound of claim 1 wherein at least one R14 is L1 and at least one R14 is L2.10. The oligomeric compound of claim 1 comprising from 8 to about 30 nucleosides.11. The oligomeric compound of claim 1 comprising from 15 to about 25 nucleosides.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (144)
Tkachuk Zenovy (Kiev SUX) Kvasyuk Eugeny (Kiev SUX) Matsuka Gennady (Kiev SUX) Mikhailopulo Igor (Kiev SUX), (2′-5′) oligoadenylate analogues useful as inhibitors of host-v5.-graft response.
Huynh Dinh Tam (Croissy/Seine FRX) Gouyette Catherine (Vanves FRX) Igolen Jean (Le Mesnil St. Denis FRX), 2,N6-disubstituted and 2,N6-trisubstituted adenosine-3′-phosphoramidites.
Suhadolnik Robert J. (Roslyn PA) Pfleiderer Wolfgang (Constance DEX), 2′,5′-phosphorothioate oligoadenylates and their covalent conjugates with polylysine.
Cook Philip D. (Carlsbad CA) Delecki Daniel J. (Radnor PA) Guinosso Charles (Vista CA), Acyclic nucleoside analogs and oligonucleotide sequences containing them.
Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR) Stirchak Eugene P. (Corvallis OR), Alpha-morpholino ribonucleoside derivatives and polymers thereof.
Crooke Stanley T. (Carlsbad CA) Mirabelli Christopher K. (Encinitas CA) Ecker David J. (Carlsbad CA) Cowsert Lex M. (Carlsbad CA), Antisense oligonucleotide inhibition of papillomavirus.
Crooke Stanley T. (Carlsbad CA) Mirabelli Christopher K. (Encinitas CA) Ecker David J. (Carlsbad CA) Cowsert Lex M. (Carlsbad CA), Antisense oligonucleotides directed to papillomavirus.
Draper Kenneth G. (San Marcos CA) Ecker David J. (Carlsbad CA) Mirabelli Christopher K. (Encinitas CA) Crooke Stanley T. (Carlsbad CA), Antisense oligonucleotides for inhibiting herpesviruses.
Lima Walter (San Diego CA) Monia Brett (Carlsbad CA) Freier Susan (San Diego CA) Ecker David (Leucadia CA), Antisense oligonucleotides to the RAS gene.
Sanghvi Yogesh S. (Carlsbad CA) Cook Phillip D. (Carlsbad CA), Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling.
Cook Phillip D. (Carlsbad CA) Sanghvi Yogesh S. (San Marcos CA) Vasseur Jean J. (San Marcos CA) Debart Francoise (Montpellier FRX), Backbone modified oligonucleotide analogues.
Sanghvi Yogesh S. (San Marcos CA) Cook Phillip D. (Vista CA), Backbone-modified oligonucleotide analogs and preparation thereof through radical coupling.
Spielvogel Bernard F. (Raleigh NC) Sood Anup (Durham NC) Hall Iris H. (Chapel Hill NC) Ramsay Shaw Barbara (Durham NC), Boronated nucleoside, nucleotide and oligonucleotide compounds, compositions and methods for using same.
Altmann Karl-Heinz (Basel CHX) Imwinkelried Rene (Brig-Glis CHX) Eschenmoser Albert (Kusnacht CHX), Carbocyclic nucleosides containing bicyclic rings, oligonucleotides therefrom, process for their preparation, their use.
Altmann Karl-Heinz (Basel CHX) Imwinkelried Rene (Brig-Glis CHX) Eschenmoser Albert (Kusnacht CHX), Carbocyclic nucleosides containing bicyclic rings, oligonucleotides therefrom, process for their preparation, their use.
Andrus William A. (San Francisco CA) Efcavitch J. William (Belmont CA) McBride Lincoln J. (Redwood City CA), Chemical capping by phosphitylation during oligonucleotide synthesis.
Bertsch-Frank Birgit (Rheinfelden DEX) Klasen Claas-Juergen (Freigericht DEX) Lieser Thomas (Hapau DEX) Mueller Klaus (Hasselroth DEX) Bewersdorf Martin (Gelnhausen DEX), Coated sodium percarbonate particles, a process for their production and detergent, cleaning and bleaching compositions.
Baxter Anthony D. (Northwich GB2) Baylis Eric K. (Stockport GB2) Collingwood Stephen P. (Westhoughton GB2) Taylor Roger J. (Stretford GB2) De Mesmaeker Alain (Kanerkinden CHX) Schmit Chantal (Basel C, Dinucleoside phosphinates and their pharmaceutical compositions.
Froehler Brian (Belmont CA) Matteucci Mark (Burlingame CA), Enhanced triple-helix and double-helix formation with oligomers containing modified purines.
Rogers Thomas E. (Manchester MO) Gray Steven H. (Ellisville MO) Devadas Balekudru (Chesterfield MO) Adams Steven P. (St. Charles MO), Improved probes using nucleosides containing 3-dezauracil analogs.
Agrawal Sudhir (Shrewsbury MA) Leiter Josef M. E. (Brooklyn NY) Palese Peter (Leonia NJ) Zamecnik Paul C. (Shrewsbury MA), Inhibition of influenza virus replication by oligonucleotide phosphorothioates.
Cohen Jack S. (Bethesda MD) Neckers Len (Bethesda MD) Stein Cy (Gaithersburg MD) Loke She L. (Wheaton MD) Shinozuka Kazuo (Kazo JPX), Inhibitors for replication of retroviruses and for the expression of oncogene products.
Cohen Jack S. (Bethesda MD) Neckers Len (Bethesda MD) Stein Cy (Gaithersburg MD) Loke She L. (Wheaton MD) Shinozuka Kazuo (Kazo JPX), Inhibitors for replication of retroviruses and for the expression of oncogene products.
Cohen Jack S. (Bethesda MD) Neckers Len (Bethesda MD) Stein Cy (Gaithersburg MD) Loke Shee L. (Wheaton MD) Shinozuka Kazuo (Kazo JPX), Inhibitors for replication of retroviruses and for the expression of oncogene products.
Chu Chung K. ; Cheng Yung-Chi ; Pai Balakrishna S. ; Yao Gang-Qing, L-nucleosides incorporated into polymeric structure for stabilization of oligonucleotides.
Benner Steven A. (Hadlaubstrasse 151 CH-8006 Zurich CHX), Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases.
Matteucci Mark (Burlingame CA) Jones Robert J. (Daly City CA) Munger John (San Francisco CA), Modified internucleoside linkages having one nitrogen and two carbon atoms.
Ts\o Paul O. P. (2117 Folkstone Rd. Lutherville MD 21093) Miller Paul S. (225 Hopkins Rd. Baltimore MD 21212), Nonionic nucleic acid alkyl and aryl phosphonates and processes for manufacture and use thereof.
Cook Philip D. (Carlsbad CA) Sanghvi Yogesh S. (San Marcos CA), Nuclease resistant, pyrimidine modified oligonucleotides that detect and modulate gene expression.
Boggs Russell T. (Cardiff-by-the-Sea CA) Dean Nicholas M. (Cardiff-by-the-Sea CA), Nucleic acid sequences encoding protein kinase C and antisense inhibition of expression thereof.
Meyer ; Jr. Rich B. (Woodinville WA) Adams A. David (Snohomish WA) Petrie Charles R. (Woodinville WA), Oligo (aa
상세보기
Letsinger Robert L. (Wilmette IL) Gryaznov Sergei M. (San Mateo CA), Oligodeoxyribonucleotides including 3′-aminonucleoside-phosphoramidate linkages and terminal 3′-amino groups.
Bischofberger Norbert (San Carlos CA) Kent Ken (Mountain View CA) Wagner Rick (Burlingame CA) Buhr Chris (Daly City CA) Lin Kuei-Ying (Fremont CA), Oligonucleotide analogs capable of passive cell membrane permeation.
Weis Alexander Ludvik (Berwyn PA) Hausheer Frederick Herman (San Antonio TX) Chaturvedula Prasad Venkata Chala (Exton PA) Delecki Daniel Joseph (Radnor PA) Cavanaugh ; Jr. Paul Francis (West Chester , Oligonucleotide analogues containing phosphate diester linkage substitutes, compositions thereof, and precursor dinucleo.
Draper Kenneth G. (Boulder CO) Crooke Stanley T. (Carlsbad CA) Mirabelli Christopher K. (Encinitas CA) Ecker David J. (Leucadia CA) Hanecak Ronnie C. (San Clemente CA) Anderson Kevin P. (Carlsbad CA), Oligonucleotide therapies for modulating the effects of herpes viruses.
Draper Kenneth G. (San Marcos CA) Ecker David J. (Carlsbad CA) Mirabelli Christopher K. (Encinitas CA) Crooke Stanley T. (Carlsbad CA), Oligonucleotide therapies for modulating the effects of herpesviruses.
Cook Phillip Dan (San Marcos CA) Hoke Glenn (Mt. Airy MD), Oligonucleotides for modulating Ha-ras or Ki-ras having phosphorothioate linkages of high chiral purity.
Cook Phillip D. (San Marcos CA) Hoke Glenn (Mt. Airy MD), Oligonucleotides for modulating cytomegalovirus having phosphorothioate linkages of high chiral purity.
Cook Phillip D. (San Marcos CA) Hoke Glenn (Mt. Airy MD), Oligonucleotides for modulating protein kinase C having phosphorothioate linkages of high chiral purity.
Anderson Kevin (Carlsbad CA) Draper Kenneth (Boulder CO) Baker Brenda (Encinitas CA), Oligonucleotides for modulating the effects of cytomegalovirus infections.
Smith Lloyd M. (South Pasadena CA) Fung Steven (Palo Alto CA) Kaiser ; Jr. Robert J. (Glendale CA), Oligonucleotides possessing a primary amino group in the terminal nucleotide.
Lebleu Bernard (Montpellier FRX) Bayard Bernard (Castelnau Le Lez FRX), Oligonucleotides with modified phosphate and modified carbohydrate moieties at the respective chain termini.
Imbach Jean-Louis (Montpellier FRX) Gosselin Gilles J. M. (Montpellier FRX), Oligonucleotides, a process for preparing the same and their application as mediators of the action of interferon.
Spielvogel Bernard F. (Raleigh NC) Sood Anup (Durham NC) Hall Iris H. (Chapel Hill NC) Shaw Barbara R. (Durham NC), Oligoribonucleoside and oligodeoxyribonucleoside boranophosphates.
Misiura Konrad (Lodz PLX) Gait Michael (Cambridge GB3), Phosphoramidite derivatives, their preparation and the use thereof in the incorporation of reporter groups on synthetic.
Maddry Joseph A. (Birmingham AL) Reynolds Robert C. (Birmingham AL) Secrist John A. (Birmingham AL) Montgomery John A. (Birmingham AL) Crooks Peter A. (Lexington KY), Polynucleotide analogs containing sulfonate and sulfonamide internucleoside linkages.
Caruthers Marvin H. (Boulder CO) Marshall William S. (Boulder CO) Brill Wolfgang (Freiburg DEX) Nielsen John (Horsholm DKX), Polynucleotide phosphorodithioate.
Urdea Michael S. (Alamo CA) Horn Thomas (Berkeley CA), Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use.
Hawkins Mary E. (Potomac MD) Pfleiderer Wolfgang (Konstanz MD DEX) Davis Michael D. (Rockville MD) Balis Frank (Bethesda MD), Pteridine nucleotide analogs as fluorescent DNA probes.
Van Ness Jeffrey (Bothell WA) Petrie Charles R. (Woodinville WA) Tabone John C. (Bothell WA) Vermeulen Nicolaas M. J. (Woodinville WA), Solid supports for nucleic acid hybridization assays.
Cook Phillip Dan (Carlsbad CA) Manoharan Muthiah (Carlsbad CA) Ramasamy Kanda S. (Laguna Hills CA), Substituted purines and oligonucleotide cross-linking.
Summerton James E. (Corvallis OR) Weller Dwight D. (Corvallis OR), Uncharged morpolino-based polymers having phosphorous containing chiral intersubunit linkages.
Gryaznov, Sergei M.; Zielinska, Daria; Pruzan, Ronald A.; Lindquist, Jeffrey N., C-myc antisense oligonucleotides and methods for using the same to treat cell-proliferative disorders.
Gryaznov, Sergei M.; Zielinska, Daria; Pruzan, Ronald A.; Lindquist, Jeffrey N., C-myc antisense oligonucleotides and methods for using the same to treat cell-proliferative disorders.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of Adiponectin (ADIPOQ) related diseases by inhibition of natural antisense transcript to an Adiponectin (ADIPOQ).
Collard, Joseph; Khorkova Sherman, Olga, Treatment of Methionine sulfoxide reductase a (MSRA) related diseases by inhibition of natural antisense transcript to MSRA.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of adiponectin (ADIPOQ) related diseases by inhibition of natural antisense transcript to an adiponectin (ADIPOQ).
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos; Shen, Gang, Treatment of alpha-L-iduronidase (IDUA) related diseases by inhibition of natural antisense transcript to IDUA.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos; Shen, Gang, Treatment of alpha-L-iduronidase (IDUA) related diseases by inhibition of natural antisense transcript to IDUA.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of antiviral gene related diseases by inhibition of natural antisense transcript to an antiviral gene.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of atonal homolog 1 (ATOH1) related diseases by inhibition of natural antisense transcript to ATOH1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of atonal homolog 1 (ATOH1) related diseases by inhibition of natural antisense transcript to ATOH1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of atonal homolog 1 (ATOH1) related diseases by inhibition of natural antisense transcript to ATOH1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of atonal homolog 1 (ATOH1) related diseases by inhibition of natural antisense transcript to ATOH1.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos, Treatment of brain derived neurotrophic factor (BDNF) related diseases by inhibition of natural antisense transcript to BDNF.
Faghihi, Mohammad Ali; Coito, Carlos, Treatment of brain derived neurotrophic factor (BDNF) related diseases by inhibition of natural antisense transcript to BDNF.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of colony-stimulating factor 3 (CSF3) related diseases by inhibition of natural antisene transcript to CSF3.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of colony-stimulating factor 3 (CSF3) related diseases by inhibition of natural antisense transcript to CSF3.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of colony-stimulating factor 3 (CSF3) related diseases by inhibition of natural antisense transcript to CSF3.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos, Treatment of delta-like 1 homolog (DLK1) related diseases by inhibition of natural antisense transcript to DLK1.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos, Treatment of delta-like 1 homolog (DLK1) related diseases by inhibition of natural antisense transcript to DLK1.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos, Treatment of discs large homolog (DLG) related diseases by inhibition of natural antisense transcript to DLG.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos, Treatment of discs large homolog (DLG) related diseases by inhibition of natural antisense transcript to DLG.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos, Treatment of discs large homolog (DLG) related diseases by inhibition of natural antisense transcript to DLG.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of down syndrome gene related diseases by inhibition of natural antisense transcript to a down syndrome gene.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of down syndrome gene related diseases by inhibition of natural antisense transcript to a down syndrome gene.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of fibroblast growth factor 21 (FGF21) related diseases by inhibition of natural antisense transcript to FGF21.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of fibroblast growth factor 21 (FGF21) related diseases by inhibition of natural antisense transcript to FGF21.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of hepatocyte growth factor (HGF) related diseases by inhibition of natural antisense transcript to HGF.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of hepatocyte growth factor (HGF) related diseases by inhibition of natural antisense transcript to HGF.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of insulin gene (INS) related diseases by inhibition of natural antisense transcript to an insulin gene (INS).
Collard, Joseph; Khorkova Sherman, Olga, Treatment of insulin receptor substrate 2 (IRS2) related diseases by inhibition of natural antisense transcript to IRS2 and transcription factor E3 (TFE3).
Collard, Joseph; Khorkova Sherman, Olga, Treatment of interferon regulatory factor 8 (IRF8) related diseases by inhibition of natural antisense transcript to IRF8.
Collard, Joseph; Sherman, Olga Khorkova, Treatment of interferon regulatory factor 8 (IRF8) related diseases by inhibition of natural antisense transcript to IRF8.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of membrane bound transcription factor peptidase, site 1 (MBTPS1) related diseases by inhibition of natural antisense transcript to MBTPS1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of membrane bound transcription factor peptidase, site 1 (MBTPS1) related diseases by inhibition of natural antisense transcript to MBTPS1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of methionine sulfoxide reductase a (MSRA) related diseases by inhibition of natural antisense transcript to MSRA.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos, Treatment of nuclear factor (erythroid-derived 2)-like 2 (NRF2) related diseases by inhibition of natural antisense transcript to NRF2.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of nuclear respiratory factor 1 (NRF1) related diseases by inhibition of natural antisense transcript to NRF1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of nuclear respiratory factor 1 (NRF1) related diseases by inhibition of natural antisense transcript to NRF1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of pancreatic developmental gene related diseases by inhibition of natural antisense transcript to a pancreatic developmental gene.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of pancreatic developmental gene related diseases by inhibition of natural antisense transcript to a pancreatic developmental gene.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of pyrroline-5-carboxylate reductase 1 (PYCR1) related disease by inhibition of natural antisense transcript to PYCR1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of pyrroline-5-carboxylate reductase 1 (PYCR1) related diseases by inhibition of natural antisense transcript to PYCR1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of pyrroline-5-carboxylate reductase 1 (PYCR1) related diseases by inhibition of natural antisense transcript to PYCR1.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of reprogramming factor related diseases by inhibition of natural antisense transcript to a reprogramming factor.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of sex hormone binding globulin (SHBG) related diseases by inhibition of natural antisense transcript to SHBG.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos; De Leon, Belinda, Treatment of sirtuin (SIRT) related diseases by inhibition of natural antisense transcript to a sirtuin (SIRT).
Collard, Joseph; Khorkova Sherman, Olga; De Leon, Belinda; Coito, Carlos; Hsiao, Jane H., Treatment of sodium channel, voltage-gated, alpha subunit (SCNA) related diseases by inhibition of natural antisense transcript to SCNA.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of transcription factor E3 (TFE3) and insulin receptor substrate 2 (IRS2) related diseases by inhibition of natural antisense transcript to TFE3.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of transcription factor E3 (TFE3) and insulin receptor substrate 2(IRS2) related diseases by inhibition of natural antisense transcript to TFE3.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of tumor necrosis factor receptor 2 (TNFR2) related diseases by inhibition of natural antisense transcript to TNFR2.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of tumor necrosis factor receptor 2 (TNFR2) related diseases by inhibition of natural antisense transcript to TNFR2.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of uncoupling protein 2 (UCP2) related diseases by inhibition of natural antisense transcript to UCP2.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of uncoupling protein 2 (UCP2) related diseases by inhibition of natural antisense transcript to UCP2.
Collard, Joseph; Khorkova Sherman, Olga, Treatment of vascular endothelial growth factor (VEGF) related diseases by inhibition of natural antisense transcript to VEGF.
Collard, Joseph; Sherman, Olga Khorkova, Treatment of vascular endothelial growth factor (VEGF) related diseases by inhibition of natural antisense transcript to VEGF.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos, Treatment of ‘C terminus of HSP70-interacting protein’ (CHIP)related diseases by inhibition of natural antisense transcript to CHIP.
Collard, Joseph; Khorkova Sherman, Olga; Coito, Carlos, Treatment of ‘C terminus of HSP7O-interacting protein’ (CHIP) related diseases by inhibition of natural antisense transcript to CHIP.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.