BioWorld International Correspondent

BORNHEIM, Germany - G.O.T. Therapeutics GmbH and atugen AG agreed to work on joint development of new lipid formulations, improving the knockdown of specific genes. Both Berlin-based companies will share costs and intellectual property outcomes of the project.

Functional genomics specialist atugen knocks down genes by proprietary GeneBloc molecules, which are small, synthetic DNA/RNA hybrid molecules that bind to a specific target messenger RNA and induce its enzymatic destruction by an RNAase. Changes in function then can be correlated with the loss of the specific messenger RNA and protein and, therefore, gene function, atugen said. Since the technique is reversible, restoration of function provides proof that inhibition was specific and no deleterious effects were made to the cell.

"Using GeneBlocs we are sure that we really knock down a specific gene, rather than inducing nonspecific effects that can cause toxic effects," Zisi Fotev, the company's vice president, business development, told BioWorld International, adding that such toxicity commonly occurs when antisense molecules are combined with commercially available lipids.

"We currently use about 500 different lipids to deliver GeneBlocs into the cell and the nucleus," Fotev said. "These lipids are cell-type specific and provide a five-day long-term knockdown of the wanted gene. Following application, approximately half of the lipids carrying GeneBloc remain on the cell membrane, 25 percent stay in the cytoplasm and 25 percent reach the nucleus, where they knock out their target genes.

"Our standard transfection rates are 70 percent at minimum," Fotev said. However, certain types of cells, such as hemopoietic cells, are relatively resistant to high transfection rates. "There are hundreds of potential target genes of interest for the pharmaceutical industry in T lymphocytes, for example, but up to now you could not reach them sufficiently. By targeting them with G.O.T.-liposomed GeneBloc, we aim to improve the current knockdown rates we obtain in these cell types on target genes of 50 [percent] to 90 percent, which in effect is already sensational."

G.O.T. will retain exclusive use in DNA-based therapy, while atugen will retain all other rights such as target discovery, validation and therapeutic use with GeneBloc molecules, atugen said.

"Our liposomes are stable enough to resist degradation and protect the GeneBlocs from degradation," G.O.T. CEO Regina Reszka told BioWorld International, adding that G.O.T. wants to further improve the liposomes, tailoring them for each application. The company also performs full chemical analysis and characterization of the lipids involved. "We also will investigate whether the lipids themselves enhance or inhibit the gene knockout."

G.O.T. also provides liposomes for nonviral gene transfer, a technology in Phase I/II trials for treatment of certain brain tumors.

G.O.T. intends to generate revenues by developing tailored capsulation of cytostatic drugs, such as carboplatin, for treatment of head, neck and urogenital tumors to reduce therapy-limiting side effects of the drugs, and taxol, being used for treating breast cancer. "There is some evidence that taxol also is efficient against tumors in the peritoneum and abdominal cancer, if delivered in a liposome ferry," Reszka said.

Reszka founded G.O.T. in 1997, spinning off Berlin-based Max Delbr|ck Center for Molecular Medicine. Its seed financing of DM4 million was provided by government grants and Mediport Venture Funds, of Berlin.