RNAi-based New Therapeutic Strategies against Anthrax

Technology #d-0885

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Researchers
Mingtao Zeng
We are developing new-generation vaccines against human respiratory pathogens such as influenza viruses, Streptococcus pneumoniae, nontypeable Haemophilus influenzae (NTHi), and agents important for biodefense such as Bacillus anthracis, botulinum neurotoxins, and Francisella tularensis.
External Link (elpaso.ttuhsc.edu)
Maria T Arevalo
Managed By
David Snow
Director Intellectual Property 806-834-4989
Patent Protection

PCT Patent Application Filed
Publications
Detoxified lethal toxin as a potential mucosal vaccine against anthrax.
PubMed,
Protection against anthrax by needle-free mucosal immunization with human anthrax vaccine.
PubMed,
Transcriptional stimulation of anthrax toxin receptors by anthrax edema toxin and Bacillus anthracis Sterne spore.
PubMed,
Files and Attachments
Zeng_Attachment_Manuscript_3.18.12.pdf [PDF]

The technology has the potential to be used by military personnel to fight bioterrorist attacks.

Anthrax spores can be aerosolized and dispersed as a bioweapon.  Post-exposure treatment for inhalational anthrax is available, but unreliable at later stages of infection when high levels of anthrax toxins are present.  Anthrax toxins enter cells via two identified anthrax toxin receptors: tumor endothelial marker 8 and capillary morphogenesis protein 2.  Thus, it was sought to block entry of anthrax toxins into murine macrophages by silencing anthrax toxin receptors using RNAi technology.  Results show that silencing of capillary morphogenesis protein 2 using targeted siRNAs provides almost complete protection against cytotoxicity and death induced by anthrax lethal toxin as determined by viability assay.  The same results were obtained by prebinding cells with specific antibody prior to treatment with anthrax lethal toxin.  Thus, have identified capillary morphogenesis 2-targeted RNAi technology as a potential life-saving therapy following infection with anthrax.


Features, Benefits & Advantages:

The technology uses a novel RNA interference (RNAi) strategy to target several important host factors in order to block toxin endocytosis and the downstream over expression of proinflammatory cytokines induced by anthrax toxins.


Development Stage:

The technology has been produced and tested.  Preliminary experimental data have provided proof of concept.