Turning Antisense into Therapeutics

Antisense is a fascinating concept for treating a wide variety of diseases. It prevents the formation of disease-triggering proteins, which is a profound contrast to conventional drugs that have to fight against the activity of these proteins.

How does antisense work? DNA carries the genetic information of life in cells. This information is transcribed into RNA, which acts as a “blue print” for the production of proteins, no matter if the genetic information is human, herbal, bacterial or viral. By binding to the messenger RNA (mRNA), antisense drugs block “DNA’s” genetic information from transforming into disease triggering proteins. 

Antisense can be used to combat a vast number of diseases like viral infections, cancer or inflammations and has the potential to be a new magic bullet. However in practice, so far none of the existing antisense concepts provide sufficient uptake into living cells. Delivery is the last obstacle of turning antisense into therapeutics up to now. ugichem´s new generation of antisense drugs, the CMCOs (Cell Membrane Crossing Oligomers) are unique among all competing antisense concepts because they penetrate into cells without needing any additional help.

The greatest challenge for the chemical design of an antisense drug is to find an appropriate chemical structure where all important properties can be combined in one molecule: 

• Good cell penetration / delivery

• Good binding properties

• High stability

• Non-toxicity

• No immune system stimulation

• High sequence specificity

• Manifold options for chemical modifications

In the end, all biological or biochemical properties of an antisense drug result from the composition of the corresponding chemical functionalities. Consequently, the development of a successfull antisense drug is primarily a question of chemistry.

As a consequence, it is essential that the basic chemical structure of an antisense drug allows manifold options for chemical modifications. Most antisense chemistries are based on the pattern of natural RNA. However, the possibilities of chemical modifications within the RNA backbone are limited. Furthermore, the RNA backbone has been optimized by nature for millions of years. Hence, chemical modifacation of the RNA backbone must automatically result in the emergence of adverse properties. Because of these facts it has turned out that the development of RNA based antisense drugs is very challenging.

In contrast to others, ugichem`s approach to antisense drug development is purely from  a chemist`s point of view. We have identified and combined the necessary chemical functionalities in one molecule, taking under consideration to keep the chemical structure of antisense drugs as simple as possible.

In summary, CMCOs comprise many important characteristics, making them unique and partly unrivalled among the different antisense chemistries.

• CMCOs have manifold options for chemical modifications

• CMCOs penetrate into cells without additional help

• CMCOs are highly mobile inside the cells

• CMCOs have a high water solubility

• CMCOs have low toxicity

• CMCOs are stable against enzymatic degradation

• CMCOs bind to RNA with a high specificity