A self-assembling short oligonucleotide duplex suitable for pretargeting Journal Article

Authors: Mallikaratchy, P.; Gardner, J.; Nordstrøm, L. U. R.; Veomett, N. J.; McDevitt, M. R.; Heaney, M. L.; Scheinberg, D. A.
Article Title: A self-assembling short oligonucleotide duplex suitable for pretargeting
Abstract: 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. © 2013, Mary Ann Liebert, Inc.
Journal Title: Nucleic Acid Therapeutics
Volume: 23
Issue: 4
ISSN: 2159-3337
Publisher: Mary Ann Liebert, Inc  
Date Published: 2013-08-01
Start Page: 289
End Page: 299
Language: English
DOI: 10.1089/nat.2013.0425
PROVIDER: scopus
PMCID: PMC3723235
PUBMED: 23848521
Notes: --- - "Export Date: 4 September 2013" - "Source: Scopus"
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MSK Authors
  1. Mark L Heaney
    85 Heaney
  2. Michael R Mcdevitt
    117 Mcdevitt
  3. Jeffrey Gardner
    32 Gardner
  4. Nicholas J Veomett
    10 Veomett