AptaMed, Inc. is the world leader in and exclusive supplier of "thioaptamers", high affinity oligonucleotide agents that can be targeted to virtually any protein including human cytokines, transcription factors and viral proteins, with the aim of developing break-through diagnostics and therapeutics.  Thioaptamers are selectively functionalized oligonucleotides containing sulfur modifications at specific internucleoside phosphoryl sites that impart unprecedented nuclease resistance, stability, target affinity and selectivity.  Thioaptamers can be used in virtually any application that might be addressed with antibodies without all the disadvantages associated with the handling or storage of proteins.

AptaMed, Inc. has exclusive license to the thioaptamer technologies developed in Professor David Gorenstein’s laboratories at the University of Texas Medical Branch (UTMB) in Galveston, Texas.  Developed at UTMB as a keystone technology in their Biodefense countermeasures research originally funded by DARPA, then extensively expanded by DARPA, DTRA, DHS, and NIH-funding, the thioaptamer technology offers significant advantages for innovative solutions in infectious disease and cancer, to name only two.

To date, we have focused our efforts on developing phosphoromonothioate (S-ODN) and phosphorodithioate (S2-ODN) oligodeoxynucleotide thioaptamers targeting transcription factors such as NF-kB and AP-1 as well as other biomolecules important in infectious disease and cancer. Several of our thioaptamers are currently in pre-clinical development as therapeutics for viral diseases such as West Nile virus and arenavirus hemorrhagic fevers. As part of this large-scale effort, AptaMed has been aggressively developing novel technologies for high-throughput screening and bead-based combinatorial libraries of thioaptamers.

AptaMed Thioaptamer Technology

Thioaptamers (TAs) are RNA or DNA single-strand or double-strand oligonucleic acids. RNA and DNA oligonucleotides (ODNs) have been demonstrated to bind to various proteins, to serve as therapeutic or diagnostic reagents, and to investigate the specific role of transcription factors in regulating the expression of genes. In contrast to antisense agents, aptamers appear to exhibit few if any non-specific effects.  Our founders have helped develop an important class of sulfur-containing oligonucleotides, the dithiophosphate S2-ODNs (Farschtschi & Gorenstein, 1988). This is the first patent awarded for this class of agent (U.S. Patent 5,218,088, 1993; see also Gorenstein, et al., U.S. Patent, #6,423,493, 2002 and Patents Pending), all of which are exclusively licensed to AptaMed).  The dithioates contain an internucleotide phosphodiester group with sulfur substituted for both nonlinking phosphoryl oxygens, so they are both isosteric and isopolar with the normal phosphodiester link, and are also highly nuclease resistant.  Significantly, the S2-ODNs, in contrast to the phosphoramidite-synthesized monothiophosphate (S-ODNs), are achiral about the dithiophosphate center, so problems associated with diastereomeric mixtures are completely avoided.  Importantly, it has been noted that sulfur substitutions of the phosphoryl oxygens of oligonucleotides often leads to their enhanced binding to numerous proteins.  However, there is the need to optimize the total number of thioated phosphates to decrease non-specific binding to non-target proteins, and to enhance only the specific favorable interactions with the target protein.  The task becomes how to determine which phosphates to substitute in a specific ODN sequence in order to develop a thioaptamer which retains the highest specificity in binding to its target protein and yet is stable in vivo.

At AptaMed we are developing new, massively parallel, thioaptamer bead-based high-throughput screening to select target-specific thioaptamers as well as siRNA thioaptamers. AptaMed has exclusive license to our recently developed split and pool synthesis combinatorial chemistry method for creating a combinatorial library of thioated oligonucleotide agents (either phosphate, monothiophosphate, dithiophosphate or hybrid backbone (Gorenstein et al, US Patents pending, Yang et al., 2002b, 2003)). In this procedure, each unique member of the combinatorial library is attached to a separate support bead. Targets that bind tightly to only a few of the 100s of millions of different support beads can then be selected by binding the target protein to the beads, then identifying which beads have bound target by immunostaining techniques or direct staining of the target. Our methodology allows us to rapidly screen at rates of up to a billion beads/hr and identify thioaptamers that bind to proteins using a novel PCR-based identification tag of the selected bead (Yang et al., 2002, 2003).

• Thioaptamers can be selected for virtually any protein or nucleic acid, carbohydrates, and many small molecules.
• They can be used for bead assays, cell-based assays, or whole animal imaging.
• We can provide combinatorial libraries of thioaptamer beads utilizing latex beads (20 mm as well as 65 mm diameter).
• Thioaptamers can be provided with 5' or 3' amino, thiol ester, biotin or other linker chemistries for attachment to any modified bead of interest (such as Bio-Plex beads).
• Our technology gives us the ability to rapidly identify new TAs that have affinities and selectivities comparable to Mab's at lower cost, higher storage stability and biological stability in fluids.
• In many applications, properly optimized TAs can approach and even surpass the binding characteristics of antibodies.
• TAs are chemically synthesized giving them the advantage of being inherently less costly to produce than antibodies.

Contact Us

• David Gorenstein, Ph.D.
  Founder and Chairman
  (281) 851-7785
  david@aptamed.com

• Bruce Luxon, Ph.D.
  President and Co-founder
  (409) 771-0207
  bruce@aptamed.com
  
  
• Mailing Address:
  AptaMed, Inc.
  18 Cedar Lawn Circle
  Galveston, TX 77551