A self-assembling short oligonucleotide duplex suitable for pretargeting

Nucleic Acid Ther. 2013 Aug;23(4):289-99. doi: 10.1089/nat.2013.0425. Epub 2013 Jul 13.


Monoclonal antibodies (mAbs) have naturally evolved as suitable, high affinity and specificity targeting molecules. However, the large size of full-length mAbs yields poor pharmacokinetic properties. A solution to this issue is the use of a multistep administration approach, in which the slower clearing mAb is administered first and allowed to reach the target site selectively, followed by administration of a rapidly clearing small molecule carrier of the cytotoxic or imaging ligand, which bears a cognate receptor for the mAb. Here, we introduce a novel pretargetable RNA based system comprised of locked nucleic acids (LNA) and 2'O-Methyloligoribonucleotides (2'OMe-RNA). The duplex shows fast hybridization, high melting temperatures, excellent affinity, and high nuclease stability in plasma. Using a prototype model system with rituximab conjugated to 2'OMe-RNA (oligo), we demonstrate that LNA-based complementary strand (c-oligo) effectively hybridizes with rituximab-oligo, which is slowly circulating in vivo, despite the high clearance rates of c-oligo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific / administration & dosage
  • Antibodies, Bispecific / chemistry*
  • Antibodies, Bispecific / immunology
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage
  • Antibodies, Monoclonal, Murine-Derived / chemistry
  • Female
  • Half-Life
  • Indium Radioisotopes
  • Mice
  • Mice, SCID
  • Molecular Targeted Therapy / methods*
  • Nucleic Acid Conformation
  • Nucleic Acid Hybridization
  • Oligonucleotides / administration & dosage
  • Oligonucleotides / chemistry*
  • Oligonucleotides / genetics
  • Oligonucleotides, Antisense / administration & dosage
  • Oligonucleotides, Antisense / chemical synthesis*
  • Oligonucleotides, Antisense / genetics
  • Oligoribonucleotides / administration & dosage
  • Oligoribonucleotides / chemical synthesis*
  • Oligoribonucleotides / genetics
  • RNA Stability
  • Radioligand Assay
  • Rituximab


  • Antibodies, Bispecific
  • Antibodies, Monoclonal, Murine-Derived
  • Indium Radioisotopes
  • Oligonucleotides
  • Oligonucleotides, Antisense
  • Oligoribonucleotides
  • locked nucleic acid
  • Rituximab