DE18203666T1 - Modifizierte polynukleotide zur herstellung von sekretierten proteinen - Google Patents

Modifizierte polynukleotide zur herstellung von sekretierten proteinen Download PDF

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Publication number
DE18203666T1
DE18203666T1 DE18203666.5T DE18203666T DE18203666T1 DE 18203666 T1 DE18203666 T1 DE 18203666T1 DE 18203666 T DE18203666 T DE 18203666T DE 18203666 T1 DE18203666 T1 DE 18203666T1
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DE
Germany
Prior art keywords
polynucleotide
composition
methylpseudouridine
interaction partner
toll
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
DE18203666.5T
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English (en)
Inventor
Stephane Bancel
Tirtha Chakraborty
Antonin De Fougerolles
Sayda M. ELBASHIR
Matthias John
Atanu Roy
Susan Whoriskey
Kristy M. WOOD
Paul Hatala
Jason P. SCHRUM
Kenechi Ejebe
Jeff Lynn Ellsworth
Justin Guild
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
ModernaTx Inc
Original Assignee
ModernaTx Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=49235350&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=DE18203666(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by ModernaTx Inc filed Critical ModernaTx Inc
Publication of DE18203666T1 publication Critical patent/DE18203666T1/de
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
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    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
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Abstract

Zusammensetzung, umfassend ein modifiziertes mRNA-Polynukleotid, das für ein Polypeptid von Interesse codiert und N1-Methylpseudouridin umfasst, zur Verwendung in einem Verfahren zum Behandeln oder Vorbeugen einer Krankheit oder eines Zustands durch Herstellen des Polypeptids in vivo, wobei das modifizierte mRNA-Polynukleotid bei der Verwendung im Vergleich zu einem mRNA-Polynukleotid, das Uridin anstelle von N1-Methylpseudouridin umfasst, eine verringerte Bindungsaffinität gegenüber einem Hauptfurchen-Interaktionspartner aufweist.

Claims (9)

  1. Zusammensetzung, umfassend ein modifiziertes mRNA-Polynukleotid, das für ein Polypeptid von Interesse codiert und N1-Methylpseudouridin umfasst, zur Verwendung in einem Verfahren zum Behandeln oder Vorbeugen einer Krankheit oder eines Zustands durch Herstellen des Polypeptids in vivo, wobei das modifizierte mRNA-Polynukleotid bei der Verwendung im Vergleich zu einem mRNA-Polynukleotid, das Uridin anstelle von N1-Methylpseudouridin umfasst, eine verringerte Bindungsaffinität gegenüber einem Hauptfurchen-Interaktionspartner aufweist.
  2. In-vitro-Verfahren zum Herstellen eines Polynukleotids mit verringerter Bindung an einen Hauptfurchen-Interaktionspartner, wobei das Verfahren ein Kontaktieren einer cDNA mit einer RNA-Polymerase in Gegenwart von 1-Methylpseudouridintriphosphat umfasst, wobei das Polynukleotid im Vergleich zu einem Polynukleotid, das Uridin anstelle von N1-Methylpseudouridin umfasst, eine verringerte Bindungsaffinität gegenüber einem Hauptfurchen-Interaktionspartner aufweist.
  3. Zusammensetzung zur Verwendung nach Anspruch 1 oder Verfahren nach Anspruch 2, wobei das Polynukleotid 100 % N1-Methylpseudouridin und kein Uridin enthält.
  4. Zusammensetzung zur Verwendung nach einem der Ansprüche 1 oder 3 oder Verfahren nach einem der Ansprüche 2-3, wobei das Polynukleotid einen Poly-A-Schwanz von etwa 160 Nukleotiden umfasst.
  5. Zusammensetzung zur Verwendung nach einem der Ansprüche 1, 3 oder 4 oder Verfahren nach einem der Ansprüche 2-4, wobei das Polynukleotid ein G-Quartett am Ende des Poly-A-Schwanzes umfasst.
  6. Zusammensetzung zur Verwendung nach einem der Ansprüche 1 oder 3-5 oder Verfahren nach einem der Ansprüche 2-5, wobei das Polynukleotid eine oder mehrere microRNA-Zielsequenzen in der 3'-UTR umfasst.
  7. Verfahren nach einem der Ansprüche 2-6, wobei die RNA-Polymerase T7-RNA-Polymerase ist.
  8. Verfahren nach einem der Ansprüche 2-7, ferner umfassend die Verwendung eines Vaccinia-Capping-Enzyms.
  9. Zusammensetzung zur Verwendung nach einem der Ansprüche 1 oder 3-6 oder Verfahren nach einem der Ansprüche 2-8, wobei der Hauptfurchen-Interaktionspartner aus der Gruppe bestehend aus Toll-like-Rezeptor 3, Toll-like-Rezeptor 7, Toll-like-Rezeptor 8, einer ATPase und/oder einem Mitglied der Superfamilie-2-Klasse von DEX(D/H)-Helikasen ausgewählt ist.
DE18203666.5T 2012-04-02 2013-03-09 Modifizierte polynukleotide zur herstellung von sekretierten proteinen Pending DE18203666T1 (de)

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US201261618866P 2012-04-02 2012-04-02
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US201261618868P 2012-04-02 2012-04-02
US201261618961P 2012-04-02 2012-04-02
US201261618945P 2012-04-02 2012-04-02
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