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 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 4 September 2013" - "Source: Scopus" |
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94Heaney -
144Mcdevitt -
499Scheinberg -
34Gardner -
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