Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1995 Nov 25;23(22):4603–4607. doi: 10.1093/nar/23.22.4603

A monoclonal antibody extends the half-life of an anti-HIV oligodeoxynucleotide and targets it to CD4+ cells.

D Morelli 1, B Pozzi 1, J A Maier 1, S Ménard 1, M I Colnaghi 1, A Balsari 1
PMCID: PMC307432  PMID: 8524649

Abstract

An approach was sought to increase the half-life and target cell specificity of antisense oligodeoxynucleotides (oligos). A monoclonal antibody (MAb) was derived from mice immunised with an oligo complementary to a region (1-20) of the HIV genome. This MAb exerts a protective effect on the oligo from the degradation induced by plasma exonucleases in vitro and in vivo. Moreover the anti-oligo MAb dissociates from the oligo in the presence of its complementary sequence to allow hybridization of the two complementary strands. To direct the oligo to CD4+ cells the anti-oligo MAb was cross-linked to an anti-CD4 MAb. The heteroaggregate determines a 5-fold increase in the cellular membrane binding of the oligo to CD4+ lymphocytes. These findings suggest a new approach to enhancing the therapeutic action and the target specificity of antisense oligodeoxynucleotides useful for the selective inhibition of HIV replication in vivo.

Full text

PDF
4603

Images in this article

4605Image
on p.4605
4605Image
on p.4605
4606Image
on p.4606

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agrawal S., Goodchild J., Civeira M. P., Thornton A. H., Sarin P. S., Zamecnik P. C. Oligodeoxynucleoside phosphoramidates and phosphorothioates as inhibitors of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7079–7083. doi: 10.1073/pnas.85.19.7079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burastero S. E., Casali P., Wilder R. L., Notkins A. L. Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis. J Exp Med. 1988 Dec 1;168(6):1979–1992. doi: 10.1084/jem.168.6.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carter G., Lemoine N. R. Antisense technology for cancer therapy: does it make sense? Br J Cancer. 1993 May;67(5):869–876. doi: 10.1038/bjc.1993.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dux R., Kindler-Röhrborn A., Lennartz K., Rajewsky M. F. Determination of immunoreactive fraction and kinetic parameters of a radiolabeled monoclonal antibody in the absence of antigen excess. J Immunol Methods. 1991 Nov 22;144(2):175–183. doi: 10.1016/0022-1759(91)90084-s. [DOI] [PubMed] [Google Scholar]
  5. Eder P. S., DeVine R. J., Dagle J. M., Walder J. A. Substrate specificity and kinetics of degradation of antisense oligonucleotides by a 3' exonuclease in plasma. Antisense Res Dev. 1991 Summer;1(2):141–151. doi: 10.1089/ard.1991.1.141. [DOI] [PubMed] [Google Scholar]
  6. Frankfurt O. S. Detection of DNA damage in individual cells by flow cytometric analysis using anti-DNA monoclonal antibody. Exp Cell Res. 1987 Jun;170(2):369–380. doi: 10.1016/0014-4827(87)90314-4. [DOI] [PubMed] [Google Scholar]
  7. Gao W. Y., Han F. S., Storm C., Egan W., Cheng Y. C. Phosphorothioate oligonucleotides are inhibitors of human DNA polymerases and RNase H: implications for antisense technology. Mol Pharmacol. 1992 Feb;41(2):223–229. [PubMed] [Google Scholar]
  8. Goodchild J., Agrawal S., Civeira M. P., Sarin P. S., Sun D., Zamecnik P. C. Inhibition of human immunodeficiency virus replication by antisense oligodeoxynucleotides. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5507–5511. doi: 10.1073/pnas.85.15.5507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mantero G., Zonaro A., Albertini A., Bertolo P., Primi D. DNA enzyme immunoassay: general method for detecting products of polymerase chain reaction. Clin Chem. 1991 Mar;37(3):422–429. [PubMed] [Google Scholar]
  10. Mènard S., Tagliabue E., Canevari S., Fossati G., Colnaghi M. I. Generation of monoclonal antibodies reacting with normal and cancer cells of human breast. Cancer Res. 1983 Mar;43(3):1295–1300. [PubMed] [Google Scholar]
  11. Sarin P. S., Agrawal S., Civeira M. P., Goodchild J., Ikeuchi T., Zamecnik P. C. Inhibition of acquired immunodeficiency syndrome virus by oligodeoxynucleoside methylphosphonates. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7448–7451. doi: 10.1073/pnas.85.20.7448. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Stein C. A., Cheng Y. C. Antisense oligonucleotides as therapeutic agents--is the bullet really magical? Science. 1993 Aug 20;261(5124):1004–1012. doi: 10.1126/science.8351515. [DOI] [PubMed] [Google Scholar]
  13. Stollar B. D. Molecular analysis of anti-DNA antibodies. FASEB J. 1994 Mar 1;8(3):337–342. doi: 10.1096/fasebj.8.3.7511550. [DOI] [PubMed] [Google Scholar]
  14. Stollar B. D., Zon G., Pastor R. W. A recognition site on synthetic helical oligonucleotides for monoclonal anti-native DNA autoantibody. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4469–4473. doi: 10.1073/pnas.83.12.4469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Zaia J. A., Rossi J. J., Murakawa G. J., Spallone P. A., Stephens D. A., Kaplan B. E., Eritja R., Wallace R. B., Cantin E. M. Inhibition of human immunodeficiency virus by using an oligonucleoside methylphosphonate targeted to the tat-3 gene. J Virol. 1988 Oct;62(10):3914–3917. doi: 10.1128/jvi.62.10.3914-3917.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES