Patent · US Active

Therapeutic nucleic acid-3' -conjugates

US7910297B2 · kind B2 · utility

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4Claims
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Key dates

Filing dateFeb 15, 2005
Grant dateMar 22, 2011
Priority date
Expiry dateAug 7, 2027

Classification

  • Technology area (CPC C)Chemistry; Metallurgy
  • CPC primaryC12N2320/51
  • WIPO fieldBiotechnology
  • WIPO sectorChemistry

Abstract

Methods are described for improvement of the serum half life of therapeutic nucleic acids by 3′ conjugation to useful target proteins, or other large molecules with useful function. In one embodiment, a 3′ A, C or G overhang is added to ds-DNA and the primary amines conjugated using biocompatible bifunctional linkers to proteins. The resulting nucleic acid-3′-conjugates are serum nuclease-resistant and retained in vivo for long periods without rapid kidney clearance. Further, the choice of conjugate imparts additional functionality to the nucleic acid-3-conjugate.For example, if the protein in the DNA-protein conjugate is the first component of the complement cascade (Clq or Clqrs) and the DNA aptamer has been developed against surface components of a target cell, it can be used to treat bacterial or parasitic infections and cancers. If the protein is serum albumin or another common (nonimmunogenic) blood protein and the aptamer is directed against a toxin or venom, the aptamer-protein conjugate can be used as an antidote that binds and neutralizes the toxin or venom. Similar DNA (aptamer)-nanotube, -enzyme, and -toxin conjugates could also be used to target and selectively kill ba…

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