Health knowledge made personal
Join this community!
› Share page:
Go
Search posts:

Novel Oligonucleotides for Treatment of Human Cancer

Posted Jun 15 2010 5:00pm

Description of Invention:
Human endogenous retroviruses (HERVs) are remnants of retroviruses that invaded and integrated into the human genome 6-15 million years ago. One significant type of HERV is ERV-9; approximately 5% of the total human genome comprises sequences from this retrovirus family. The human genome contains approximately 50 copies of ERV-9 along with 3000-4000 copies of solitary elements of ERV-9 regulatory regions, called long terminal repeats (LTRs). The solitary LTRs contain promoter and enhancer elements that drive expression of genes located proximally to the LTR. Therefore, insertion of an ERV-9 LTR proximal to an oncogene could initiate carcinogenesis.

This invention relates to the use of antisense and sense oligonucleotides (oligos) targeting the RNAs of ERV-9 LTR as a treatment for various cancers, including human breast, liver, prostate, and myeloid cancers and fibrosarcomas. The inventors have shown that the ERV-9 LTR sense and antisense oligos can inhibit cancer cell proliferation in vitro more efficiently than the antisense oligos of Bcl-2 (G3139) and telomerase (GRN163), both of which are currently in cancer clinical trials. The oligos have minimal effects on the proliferation of primary normal human cells in vitro. These oligos have potential as a new therapeutic agent to suppress tumor cell growth, either when used alone or in conjunction with other antisense oligos or with chemotherapeutic agents such as VePesid. Furthermore, sense and antisense RNA transcripts of ERV-9 LTR were detected in many human normal and tumor cells in this invention. The sense and antisense RNA may form double stranded RNA and act as siRNA to regulate gene expression.

Applications:
  • Therapeutic oligos of the invention can be used to treat variety of cancers including, but not limited to, breast, liver, myeloid and prostate cancers and fibrosarcomas.
  • The oligos can be used either singly or as adjuvant therapy with chemotherapeutic agents.
  • ERV-9 LTR related cancers can be diagnosed by comparative analysis of the levels of ERV-9 LTR RNAs in tumors versus those of healthy tissues.


Advantages:
  • Greater inhibition of cell proliferation by oligos of the invention compared to the Bcl-2, telomerase and MDM2-specific antisense oligos which are currently in development as cancer therapies.
  • The therapeutic effect of the oligos is specific for cancer cells as the oligos do not significantly alter proliferation of normal human cells.


Development Status:
In vivo testing of therapeutic sense and antisense oligos in mouse xenograft models has been successfully conducted.

Inventors:
Lai Xu (FDA)
Amy S Rosenberg (FDA)
Abdel G Elkahloun (NHGRI)
Fabio Candotti (NHGRI)


Patent Status:
HHS, Reference No. E-092-2008/0
PCT, Application No. PCT/US09/056722 filed 11 Sep 2009


Relevant Publication:
  1. None related to invention have been published.


Licensing Status:
Available for licensing.


Portfolios:
Cancer
Cancer - Diagnostics
Cancer - Therapeutics
Gene Based Therapies
Gene Based Therapies - Diagnostics
Gene Based Therapies - Therapeutics
In-vivo Data
In-vitro Data



For Additional Information Please Contact:
Surekha Vathyam Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: vathyams@mail.nih.gov
Phone: 301-435-4076
Fax: 301-402-0220


Ref No: 1942

Updated: 06/2010

Post a comment
Write a comment:

Related Searches