US20080125583A1 - Ribonucleic acid interference molecules - Google Patents

Ribonucleic acid interference molecules Download PDF

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Publication number
US20080125583A1
US20080125583A1 US11/352,152 US35215206A US2008125583A1 US 20080125583 A1 US20080125583 A1 US 20080125583A1 US 35215206 A US35215206 A US 35215206A US 2008125583 A1 US2008125583 A1 US 2008125583A1
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Prior art keywords
sequences
seq
nucleic acid
acid molecule
precursor
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US11/352,152
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Isidore Rigoutsos
Tien Huynh
Kevin Charles Miranda
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GlobalFoundries Inc
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International Business Machines Corp
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Priority to US11/352,152 priority Critical patent/US20080125583A1/en
Priority to EP06720672A priority patent/EP1846433A4/fr
Priority to PCT/US2006/004949 priority patent/WO2006086739A2/fr
Priority to CA002588023A priority patent/CA2588023A1/fr
Assigned to INTERNATIONAL BUSINESS MACHINES CORPORATION reassignment INTERNATIONAL BUSINESS MACHINES CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MIRANDA, KEVIN CHARLES, HUYNH, TIEN, RIGOUTSOS, ISIDORE
Publication of US20080125583A1 publication Critical patent/US20080125583A1/en
Priority to US13/283,103 priority patent/US8445666B2/en
Assigned to GLOBALFOUNDRIES U.S. 2 LLC reassignment GLOBALFOUNDRIES U.S. 2 LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: INTERNATIONAL BUSINESS MACHINES CORPORATION
Assigned to GLOBALFOUNDRIES INC. reassignment GLOBALFOUNDRIES INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: GLOBALFOUNDRIES U.S. 2 LLC, GLOBALFOUNDRIES U.S. INC.
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G16B20/20—Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B30/00—ICT specially adapted for sequence analysis involving nucleotides or amino acids
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B40/00—ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering N.A.
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/10—Applications; Uses in screening processes
    • C12N2320/11—Applications; Uses in screening processes for the determination of target sites, i.e. of active nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2330/00—Production
    • C12N2330/10—Production naturally occurring
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B15/00—ICT specially adapted for analysing two-dimensional or three-dimensional molecular structures, e.g. structural or functional relations or structure alignment

Definitions

  • the present invention relates to genes and, more particularly, to ribonucleic acid interference molecules and their role in gene expression.
  • RNA molecules can act as potent gene expression regulators either by inducing mRNA degradation or by inhibiting translation; this activity is summarily referred to as post-transcriptional gene silencing or PTGS for short.
  • RNA interference An alternative name by which it is also known is RNA interference, or RNAi.
  • PTGS/RNAi has been found to function as a mediator of resistance to endogenous and exogenous pathogenic nucleic acids and also as a regulator of the expression of genes inside cells.
  • gene expression refers generally to the transcription of messenger-RNA (mRNA) from a gene, and its subsequent translation into a functional protein.
  • mRNA messenger-RNA
  • RNA molecules involved in gene expression regulation comprises microRNAs, which are endogenously encoded and regulate gene expression by either disrupting the translation processes or by degrading mRNA transcripts, e.g., inducing post-transcriptional repression of one or more target sequences.
  • RNAi/PTGS mechanism allows an organism to employ short RNA sequences to either degrade or disrupt translation of complementary mRNA transcripts.
  • Early studies suggested only a limited role for RNAi, that of a defense mechanism against pathogens.
  • the subsequent discovery of many endogenously-encoded microRNAs pointed towards the possibility of this being a more general, in nature, control mechanism.
  • Recent evidence has led the community to hypothesize that a wider spectrum of biological processes are affected by RNAi, thus extending the range of this presumed control layer.
  • Ribonucleic acid interference molecules are provided.
  • at least one nucleic acid molecule comprising at least one of one or more precursor sequences having SEQ ID NO: 1 through SEQ ID NO: 103,948 and one or more mature sequences having SEQ ID NO: 1 through SEQ ID NO: 126,499 is provided.
  • molecules may be one or more instances of a precursor type, one or more instances of a mature type, or some combinations thereof.
  • One or more of the sequences may be computationally predicted, e.g., from publicly available genomes, using a pattern discovery method.
  • SEQ ID NO. stands for sequence identification number. Each sequence identification number corresponds to a sequence stored in a text file on the accompanying CDROM.
  • a method for regulating gene expression comprises the following step. At least one nucleic acid molecule comprising at least one of one or more precursor sequences having SEQ ID NO: 1 through SEQ ID NO: 103,948, each one of the precursor sequences containing one or more mature sequences having SEQ ID NO: 1 through SEQ ID NO: 126,499, is used to regulate the expression of one or more genes.
  • the method may further comprise inserting the at least one nucleic acid molecule into an environment where the at least one nucleic acid molecule can be produced biochemically.
  • the method may further comprise inserting the at least one nucleic acid molecule in to an environment where the at least one nucleic acid molecule can be produced biochemically, giving rise to one or more interfering ribonucleic acids which affect one or more target sequences.
  • One or more of the sequences may be synthetically removed from the genome that contains them naturally.
  • One or more of the sequences may be synthetically introduced in a genome that does not contain them naturally.
  • One or more target sequences may be encoded by the same genome as the one or more sequences.
  • One or more target sequences may be encoded by a different genome from the one or more sequences.
  • One or more target sequences are naturally occurring.
  • One or more target sequences may be synthetically constructed.
  • One or more sequences may be transcribed, giving rise to one or more interfering ribonucleic acids which induce post-transcriptional repression of one or more target sequences.
  • One or more sequences may be transcribed, giving rise to one or more interfering ribonucleic acids which induce gene silencing of one or more target sequences.
  • One or more of the sequences may be synthetically constructed.
  • At least one nucleic acid molecule comprises at least a portion of a precursor sequence having one of SEQ ID NO: 1 through SEQ ID NO: 103,948, wherein the portion comprises an amount of the sequence that does not significantly alter a behavior of the complete precursor sequence.
  • At least one nucleic acid molecule comprises at least a portion of a mature sequence having one of SEQ ID NO: 1 through SEQ ID NO: 126,499, wherein the portion comprises an amount of the sequence that does not significantly alter a behavior of the complete mature sequence.
  • RNA molecules relate to ribonucleic acid (RNA) molecules and their role in gene expression regulation.
  • gene expression refers generally to the transcription of messenger-RNA (mRNA) from a gene, and, e.g., its subsequent translation into a functional protein.
  • mRNA messenger-RNA
  • One class of RNA molecules involved in gene expression regulation comprises microRNAs, which are endogenously encoded and regulate gene expression by either disrupting the translation processes or by degrading mRNA transcripts, e.g., inducing post-transcriptional repression of one or more target sequences.
  • microRNAs are transcribed by RNA polymerase II as parts of longer primary transcripts known as pri-microRNAs.
  • Pri-microRNAs are subsequently cleaved by Drosha, a double-stranded-RNA-specific ribonuclease, to form microRNA precursors or pre-microRNAs.
  • Pre-microRNAs are exported by Exportin-5 from the nucleus into the cytoplasm where they are processed by Dicer.
  • Dicer is a member of the RNase III family of nucleases that cleaves the pre-microRNA and forms a double-stranded RNA with overhangs at the 3′ of both ends that are one to four nucleotides long.
  • the mature microRNA is derived from either the leading or the lagging arm of the microRNA precursor.
  • a helicase separates the double-stranded RNA species into single-stranded and the strand containing the mature microRNA becomes associated with an effector complex known as RISC (for RNA-induced silencing complex).
  • RISC for RNA-induced silencing complex.
  • the RISC+microRNA construct base pairs with its target in a sequence-specific manner using Watson-Crick pairing (and the occasional formation of G:U pairs). If the microRNA is loaded into an Argonaute-2 RISC, the target is cleaved at the binding site and degraded. In the presence of mismatches between a microRNA and its target, post-transcriptional gene silencing is effected through translational inhibition.
  • the target sequence(s) may be naturally occurring.
  • the target sequences may be synthetically constructed.
  • a target sequence may be synthetically constructed so as to test prediction methods and/or to induce the RNAi/PTGS control of genes of interest.
  • a target sequence may be synthetically constructed so as to control multiple genes with a single RNA molecule, and also possibly to modify, in a combinatorial manner, the kinetics of the reaction by, for example, introducing multiple target sites.
  • the precursor sequence(s) may be either naturally occurring or synthetically constructed.
  • a precursor sequence of interest may be synthetically constructed and introduced into a cell that lacks that particular precursor.
  • they may be synthetically removed, for analysis purposes, from the genome that contains them, e.g., using standard molecular techniques.
  • the method comprises a first phase during which patterns are generated by processing an appropriate training set using a pattern discovery algorithm. If the training set comprises sequences of microRNA precursors, then the generated patterns, after appropriate attribute-based filtering, will be microRNA-precursor specific. If the training set comprises sequences of mature microRNAs, then the generated patterns, after appropriate attribute-based filtering, will be mature-microRNA specific.
  • the training set can comprise putative mature microRNAs or putative microRNA precursors. In a preferred embodiment, two training sets were used, one comprising sequences of known microRNA precursors and one comprising sequences of known mature microRNAs.
  • the basic idea of this pattern-based method is to replace the training set of sequences with an “equivalent” representation that consists of patterns.
  • the patterns can be derived using a pattern discovery algorithm, such as the Teiresias algorithm. See, for example, U.S. Pat. No. 6,108,666 issued to A. Floratos and I. Rigoutsos, entitled “Method and Apparatus for Pattern Discovery in 1-Dimensional Event Streams,” the disclosure of which is incorporated by reference herein.
  • the patterns are, ideally, maximal in composition and length (properties which are, by default, guaranteed by the Teiresias algorithm).
  • the generated microRNA-precursor-specific or mature-microRNA-specific patterns can then be used as predicates to identify, in a de novo manner, microRNA precursors from genomic sequence, or mature microRNAs in the sequence of a putative microRNA precursor. This is exploited in the method's second phase during which the patterns at hand are sought in the sequence under consideration: to determine whether a given nucleotide sequence S is part of, or encodes, a microRNA precursor the microRNA-precursor-specific patterns are used; and to determine whether a given nucleotide sequence S corresponds to, or contains a mature microRNA mature-microRNA-specific patterns are used.
  • microRNA-precursor-specific patterns in sequences that correspond to microRNA precursors whereas background and unrelated sequences should receive few or no such hits. If the number of pattern instances exceeds a predetermined threshold, then the corresponding segment of the sequence that receives the pattern support (and possibly an appropriately sized flanking region) is reported as a putative microRNA precursor. Analogous comments can be made about mature-microRNA-specific patterns and sequences containing mature microRNAs.
  • sapiens are presented; precursor sequences having SEQ ID NO: 57,432 through SEQ ID NO: 101,967 derived from the genome of M. musculus are presented; precursor sequences having SEQ ID NO: 101,968 through SEQ ID NO: 103,203 derived from the genome of D. melanogaster are presented; precursor sequences having SEQ ID NO: 103,204 through SEQ ID NO: 103,948 derived from the genome of C. elegans are presented; mature sequences having SEQ ID NO: 1 through SEQ ID NO: 69,388 derived from the genome of H. sapiens are presented; mature sequences having SEQ ID NO: 69,389 through SEQ ID NO: 124,057 derived from the genome of M.
  • musculus mature sequences having SEQ ID NO: 124,058 through SEQ ID NO: 125,536 derived from the genome of D. melanogaster are presented; and mature sequences having SEQ ID NO: 125,537 through SEQ ID NO: 126,499 derived from the genome of C. elegans are presented.
  • each precursor sequence that is listed five features are presented (in addition to the sequence ID number and the corresponding organism name).
  • the chromosome number e.g., the chromosome identifier
  • Two the precursor start and end points on the corresponding chromosome are denoted.
  • Three the strand, either forward or reverse, on which the precursor will be found, is listed.
  • the predicted folding energy also known as the energy required to denature the precursor is presented. Five, each precursor sequence is presented.
  • the chromosome number (e.g., chromosome identifier) is displayed.
  • the start and end points of the corresponding precursor sequence on the corresponding chromosome are denoted.
  • the strand, either forward or reverse, on which the corresponding precursor will be found is listed.
  • the folding energy of the corresponding precursor also known as the energy required to denature the precursor
  • the start and end points of the mature sequence on the corresponding chromosome are denoted.
  • each mature sequence is presented.
  • sequences that are either homologous or orthologous to the sequences presented herein e.g., sequences that are related by vertical descent from a common ancestor or through other means (e.g., through horizontal gene transfer), will likely be present in genomes other than the ones mentioned herein.
  • homologous/orthologous sequences are expected to generally differ from the sequences listed herein by only a small number of locations.
  • teachings presented herein should be construed as being broadly applicable to such homologous/orthologous sequences from species other than those listed above.
  • nucleic acid molecules may be generated based on the predicted precursor and mature sequences.
  • the nucleic acid molecules generated may then be used to regulate gene expression.
  • the nucleic acid molecules generated may regulate the expression of a gene, or genes, by inducing post-transcriptional silencing of the gene, e.g. as described above.
  • Using the predicted precursor and mature sequences to study gene expression may be conducted using techniques and procedures commonly known to those skilled in the art.
  • a precursor-like construct that is different than the precursor where this mature sequence naturally occurs

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US11/352,152 2005-02-11 2006-02-10 Ribonucleic acid interference molecules Abandoned US20080125583A1 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
US11/352,152 US20080125583A1 (en) 2005-02-11 2006-02-10 Ribonucleic acid interference molecules
EP06720672A EP1846433A4 (fr) 2005-02-11 2006-02-13 Molécules interférentes d'acide ribonucléique et procédés de génération de séquences de précurseur/séquences matures et de détermination de sites cibles
PCT/US2006/004949 WO2006086739A2 (fr) 2005-02-11 2006-02-13 Molecules interferentes d'acide ribonucleique et procedes de generation de sequences de precurseur/sequences matures et de determination de sites cibles
CA002588023A CA2588023A1 (fr) 2005-02-11 2006-02-13 Molecules interferentes d'acide ribonucleique et procedes de generation de sequences de precurseur/sequences matures et de determination de sites cibles
US13/283,103 US8445666B2 (en) 2005-02-11 2011-10-27 Ribonucleic acid interference molecules

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US11/352,152 US20080125583A1 (en) 2005-02-11 2006-02-10 Ribonucleic acid interference molecules

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US11/351,951 Abandoned US20060263798A1 (en) 2005-02-11 2006-02-10 System and method for identification of MicroRNA precursor sequences and corresponding mature MicroRNA sequences from genomic sequences
US11/352,152 Abandoned US20080125583A1 (en) 2005-02-11 2006-02-10 Ribonucleic acid interference molecules
US11/351,821 Abandoned US20070154896A1 (en) 2005-02-11 2006-02-10 System and method for identification of MicroRNA target sites and corresponding targeting MicroRNA sequences
US12/135,551 Expired - Fee Related US8494784B2 (en) 2005-02-11 2008-06-09 System and method for identification of microRNA target sites and corresponding targeting microRNA sequences
US13/283,103 Expired - Fee Related US8445666B2 (en) 2005-02-11 2011-10-27 Ribonucleic acid interference molecules

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US11/351,821 Abandoned US20070154896A1 (en) 2005-02-11 2006-02-10 System and method for identification of MicroRNA target sites and corresponding targeting MicroRNA sequences
US12/135,551 Expired - Fee Related US8494784B2 (en) 2005-02-11 2008-06-09 System and method for identification of microRNA target sites and corresponding targeting microRNA sequences
US13/283,103 Expired - Fee Related US8445666B2 (en) 2005-02-11 2011-10-27 Ribonucleic acid interference molecules

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EP (1) EP1846433A4 (fr)
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US20110269119A1 (en) * 2009-10-30 2011-11-03 Synthetic Genomics, Inc. Encoding text into nucleic acid sequences
US20140017780A1 (en) * 2004-05-14 2014-01-16 Rosetta Genomics Ltd MicroRNAs and uses thereof
US9536043B2 (en) 2013-03-15 2017-01-03 International Business Machines Corporation Using RNAi imaging data for gene interaction network construction
US9569584B2 (en) 2013-03-15 2017-02-14 International Business Machines Corporation Combining RNAi imaging data with genomic data for gene interaction network construction
US10358644B2 (en) 2010-11-12 2019-07-23 The General Hospital Corporation Polycomb-associated non-coding RNAs
US10858650B2 (en) 2014-10-30 2020-12-08 The General Hospital Corporation Methods for modulating ATRX-dependent gene repression
US10900036B2 (en) 2015-03-17 2021-01-26 The General Hospital Corporation RNA interactome of polycomb repressive complex 1 (PRC1)
US11066673B2 (en) 2010-11-12 2021-07-20 The General Hospital Corporation Polycomb-associated non-coding RNAs
US20220119516A1 (en) * 2019-01-16 2022-04-21 INSERM (Institut National de la Santé et de la Recherche Médicale) Variants of erythroferrone and their use
US11332745B2 (en) * 2010-08-26 2022-05-17 Sima Therapeutics, Inc. RNA interference mediated inhibition of prolyl hydroxylase domain 2 (PHD2) gene expression using short interfering nucleic acid (SINA)
WO2024102688A1 (fr) * 2022-11-07 2024-05-16 New York Society For The Relief Of The Ruptured And Crippled, Maintaining The Hospital For Special Surgery Compositions pour le traitement de troubles de l'ostéoclastogenèse et/ou de la polyarthrite rhumatoïde

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CN101348799B (zh) * 2008-07-18 2011-01-26 华中科技大学同济医学院附属同济医院 重型肝炎相关基因hfgl2 microRNA腺病毒表达质粒的构建方法及其药学用途
WO2010144058A1 (fr) 2009-06-10 2010-12-16 Temasek Life Sciences Laboratory Limited Silençage de gène induit par virus (vigs) pour l'analyse fonctionnelle de gènes dans le coton.
US8768630B2 (en) * 2010-02-19 2014-07-01 The Regents Of The University Of Michigan miRNA target prediction
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WO2016054296A2 (fr) * 2014-09-30 2016-04-07 California Institute Of Technology Compositions d'anti-vih-1 réticulé pour une neutralisation puissante et large
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US8445666B2 (en) 2013-05-21
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WO2006086739A2 (fr) 2006-08-17
EP1846433A4 (fr) 2009-09-16
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US8494784B2 (en) 2013-07-23

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