Advancing antisense chemistry has been a central focus of our research efforts. Chemical modifications can improve a drug's stability in the body, its ability to move into certain tissues and cells, its specificity and binding strength for its intended target, its side effect profile and its ability to be metabolized and eliminated from the body. Our scientists have made great advances in chemistries; building upon our first-generation technology to create antisense drugs with enhanced pharmaceutical properties, which we call our second-generation antisense drugs. We continue to advance the chemistry and design of our drugs.
Our first-generation chemistry solved many of the fundamental hurdles for creating oligonucleotide-based drugs and provided a foundation for the majority of our next-generation chemistries. First-generation antisense drugs have a sulfur chemistry modification, known as a phosphorothioate. This modification makes the drug more resistant to degradation, increases stability in the blood stream and in tissues and prevents rapid elimination of the drug from the body.
Most of the antisense drugs in our pipeline incorporate our second-generation chemistry, which adds our proprietary 2'-O-methoxyethyl (2'MOE) chemistry and makes the drugs RNA-like.
Most of our second-generation drugs are composed of both RNA-like and DNA-like nucleotides, while first-generation drugs are entirely DNA-like. Because RNA hybridizes more tightly to RNA than to DNA, the second-generation drugs have a greater affinity for their RNA targets and, therefore, greater potency. With increased potency, our second-generation drugs are active at lower doses, which decreases the overall cost of therapy.
Second-generation chemistry slows degradation of the drugs by protecting them from nucleases, the molecules responsible for disassembling strands of nucleotides. Slower clearance of the drug from the body allows for less frequent dosing. Our scientists continue to advance our technology and improve the properties of our drugs. Currently, clinicians are studying antisense drugs using many routes of delivery including enema, intrathecal, intravenous, subcutaneous, topical and intravitreal.
We have created a proprietary 'toolbox' of chemical modifications for antisense drugs that strengthen duplex formation with the target RNA and enhance the pharmaceutical properties of antisense drugs. Beyond generation 2.0 chemistry, we are evaluating entirely new types of chemistries. In 2010, we selected our generation 2.5 chemistry (cEt), an advancement that we believe will increase the potency of our drugs and make oral administration commercially feasible. We have published data demonstrating that our generation 2.5 drugs generally have enhanced potency over our generation 2.0 drugs and are broadly distributed throughout the body to multiple tissues including liver, kidney, lung, muscle, adipose, adrenal gland and peripheral nerves. Our generation 2.5 drugs constitute some of our recently added new drugs. We notate in our pipeline which drugs incorporate our generation 2.5 chemistry by appending a 2.5 at the end of the drug name. Currently ISIS-STAT3-2.5Rx, ISIS-DMPK-2.5Rx, ISIS-AR-2.5Rx, and ISIS-RHO-2.5Rx incorporate our generation 2.5 chemistry.
In addition to improving the chemical foundation of our drugs, we have also created a technology suite, LICA, designed to enhance the delivery of our drugs to particular tissues. We believe that our LICA technology could further enhance the potency of our drugs. For example, our LICA technology directed toward liver targets produced a ten-fold increase in potency in preclinical studies in both our second-generation and our generation 2.5 drugs. We currently have eight second generation-LICA drugs in our pipeline, ISIS-AGT-LRx, ISIS-ANGPTL3-LRx, ISIS-APO(a)-LRx, ISIS-APOCIII-LRx, ISIS-GHR-LRx, ISIS-GSK4-LRx, ISIS-GSK6-LRx, and ISIS-TMPRSS6-LRx. All of these drugs are designed to inhibit targets in the liver. We expect that some of our future drugs, including our generation 2.5 drugs, could also be enhanced with our LICA technology.