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GSJ: Received Mar. 2, 2007:
http://wbabin.net/saba/saba68.htm
Vaccines Comprising Small Molecule Regulated Death Genes
James Saba
Leishmania are protozoan parasites spread by a sandfly, and cause a spectrum of diseases collectively known as Leishmaniasis (1). Lesihmania infects an estimated 12 million worldwide, with 600,000 new cases per year, and 50,000 deaths per year.
Some success at vaccine development has been achieved (2,3). Particularly promising are those attenuated by genetic modification. Concerns of such genetically modified protozoan is that they can revert to wild type, and can lead to disease in those unable to mount and effect immune response.
The present invention is designed to address these concerns, and in the most preferred embodiment involves the incorporation of DNA within the protozoan which encodes a 'death-inducer' whose expression is under the control of an orally administered small molecule such as tetracycline.
Figure one exemplifies the material and methods.
As an alternative to inducing the death-gene, it is possible that its expression is repressed in the presence of a small molecule, and that upon withdrawal of this small molecule the gene is expressed.
Of course other death-inducing genes are possible. For example a nuclease, a bacterial or fungal toxin, or an iRNA directed toward the essential product of Leishmania.
Note that the materials and methods are applicable to a wide variety of vaccinations, included those directed against viruses, bacteria, fungi, and cancer cells. Futhermore, that the microbe or transformed cell need not be attenuated.
This concept was conceived and published by myself in the (no longer published) journal Icosascan in the mid 90s, but since it still appears promising it is worth reiterating.
If it should be that the above invention is indeed novel any patentable rights I may have, I freely give away.
It is hoped that others will honor the invention as delineated above and by the following claims.
2) The vaccine of claim 1 involving the regulated expression of a death-inducing product.
3) The vaccine of claim 1 wherein the microbe is a protozoan.
4) The vaccine of claim 2 wherein the protozoan is Leishmania.
5) The vaccine of claim 1 wherein the microbe is a virus.
6) The vaccine of claim 1 wherein the microbe is a bacteria.
7) The vaccine of claim 1 wherein the microbe is a fungus.
8) The vaccine of claim 1 wherein the cell is a transformed cell.
2)
Genetically modified live attenuated parasites as vaccines for
leishmaniasis.
Selvapandiyan, et al Indian J Med Res. 2006
Mar;123(3):455-66. Review.
3)
Leishmania vaccines: progress and problems.
Kedzierski, et al,Parasitology. 2006 Oct;133 Suppl:S87-S112
4)
Leishmania chagasi: A tetracycline-inducible cell line driven by T7
RNA polymerase.
Yao, et al Exp Parasitol. 2007 Jan 19
5)
A low-background inducible promoter system in Leishmania donovani.
Yan, et al Mol Biochem Parasitol. 2002 Feb;119(2):217-23
6)
Tests of cytoplasmic RNA interference (RNAi) and construction of a
tetracycline-inducible T7 promoter system in Trypanosoma cruzi.
DaRocha, et al Mol Biochem Parasitol. 2004 Feb;133(2):175-86
7)
Genetic interference in Trypanosoma brucei by heritable and
inducible double-stranded RNA.
Shi, et al RNA. 2000 Jul;6(7):1069-76
8)
Vectors for inducible expression of toxic gene products in
bloodstream and procyclic Trypanosoma brucei.
Biebinger, et al Mol
Biochem Parasitol. 1997 Mar;85(1):99-112
9)
A doubly inducible system for RNA interference and rapid RNAi
plasmid construction in Trypanosoma brucei.
Alibu , et al Mol Biochem
Parasitol. 2005 Jan;139(1):75-82
10)
A tightly regulated inducible expression system for conditional
gene knock-outs and dominant-negative genetics in Trypanosoma brucei.
Wirtz, et al Mol Biochem Parasitol. 1999 Mar 15;99(1):89-101