atugen discovers and validates therapeutic targets (in vitro/in vivo) using its proprietary KnockDown technologies (antisense i.e. GeneBloc, siRNA, Ribozymes and superior transfection reagents) for its pharmaceutical partners and its internal research and drug development programs. atugen's vision is to create new classes of therapeutics with greater selectivity and efficacy based on our unique ability to elucidate gene function and its role in diseases.
atugen’s core KnockDown technology addresses one of the major bottlenecks in drug discovery and development – identifying the right targets for therapeutic intervention. This technology is used in vitro and in vivo to destroy a specific target mRNA that would normally be translated into a protein and, hence, a biological function. Changes in function can be correlated with the loss of the specific mRNA and, therefore, gene function. As the technique is reversible, restoration of function provides proof that inhibition was specific. atugen has developed KnockDown approaches as tools for target discovery and validation (GeneBlocs and Ribozymes), which can be used in high throughput cell-based assays and in vivo.
GeneBlocs are small synthetic DNA/RNA hybrid molecules (Figure 2) that bind to a specific target mRNA and induce its destruction by RNase H. atugen has developed patented procedures to ensure that GeneBlocs are both non-toxic and stable so that they can be used in vitro and in vivo. They have also been designed to assure a very high binding affinity so that nearly all (up to 98%) target mRNA is destroyed. GeneBlocs are extremely specific and can be designed to knock down specific gene family members. This specificity is of immense value in discovering genes in complex biological pathways and allows a unique approach. GeneBlocs can be applied at different stages of development, allowing the study of genes that are active only at certain times during development. In addition, atugen has developed proprietary technology to deliver GeneBlocs to a wide variety of different cell lines, and has demonstrated in vivo functionality of GeneBlocs in cancer and diabetic models. |
atugen’s proprietary position is backed by a strong patent portfolio comprising more than 70 issued, 6 allowed and 180 pending patents. These patents cover all of atugen’s core technologies including GeneBloc technology, delivery vehicles and ribozymes. |
atugen has validated more than 200 targets for major pharmaceutical and biotechnology companies worldwide under different partner-ship agreements. The Company has also entered into strategic alliances with its partners to discover and validate targets. atugen plans to enter into more of these partnership agreements and strategic relationships, and has already started its own target discovery programs in specific therapeutic areas. |
atugen received start-up funds of $20 Mio. (BBBioVentures, tbg and various grants). It completed second financing round in July 2000 of 20 Mio. (funds advised by Apax Partners & co, BBBioVentures, tbg). |
About RNAi as Therapeutics
RNA interference (RNAi), a revolution in biology, represents a completely new approach to "silence" disease relevant genes and has the potential to become a whole new class of therapeutic products.
RNAi is a naturally occurring mechanism to destroy messenger RNA (mRNA) and thereby reduce expression of proteins involved in pathological processes. The process starts with the cleavage of input dsRNA into 19-23 base pair (bp) short interfering RNAs (siRNAs) by the enzyme Dicer in a processive and ATP-dependent manner. Noteworthy, based on the mode of action RNAi can, in principle, be used against any of the 30 - 40,000 human genes. In contrast to other classes of therapeutics such as proteins, antibodies and small molecules, RNAi requires neither "drugable" domains on the molecular target (e.g. kinase domains) nor specific locations at the cell membrane or extra-cellular.
Furthermore, siRNAs constitutes a well defined chemical entity. Even different siRNAs molecules (sequences) against the same or a different target gene will have similar ADME and toxicology/safety profiles in animals and humans. This implies that once the first siRNAs molecules have been approved for marketing by the regulatory authorities, the development and regulatory process for subsequent siRNAs molecules will be facilitated and more cost efficient. This is not the case for small molecules or antibodies, where each new chemical entity (NCE) commonly has a different composition and synthesis protocol.
The lead identification and optimization of siRNA molecules takes less than 6 months (vs. up to several years for the same process for e.g. small molecules). The significant reduction of the preclinical development time will lead to a faster way to the clinic.
Because of these advantages Science magazine has elected both the RNAi molecule and the RNAi mechanism as Molecule of the Year in 2001 and as Scientific Discovery of the Year in 2002, respectively.
Advantages of AtuRNAi
Atugen has developed novel, chemically modified proprietary siRNA. These have several advantages over conventional siRNA:
Stability against nuclease degradation resulting in longer half-life, lower doses and less frequent administration
Elimination of toxic metabolites because AtuRNAi consists of only naturally occurring building blocks
Lower manufacturing costs through cheaper building blocks and shorter oligonucleotide length (19 nucleotides)
Increased yield and faster synthesis through improved process development
Improved delivery of siRNA to target organs
Atugen has focused its in-house therapeutic development program on systemic delivery. For systemic delivery, the Company has shown in many experiments that siRNA can only be delivered to target tissues and cells when the siRNA is properly formulated with a suitable delivery vehicle. Without such a delivery vehicle, i.e. with "naked" delivery, bioavailabilty is greatly reduced and efficacy is lost. To achieve systemic delivery of AtuRNAi, Atugen has developed a proprietary liposomal delivery system, also known as lipoplex technology, called AtuPLEX, which also contains proprietary lipid components, AtuFECT.