Novel Splice Variants

Alternative splicing is a widely occurring phenomenon

Until recently, it was commonly believed that alternative splicing existed in only about 5% of all genes. However, the revised number, which was independently confirmed at Compugen, stands on at least 30% of human genes.

How do splice variants differ from the original sequence from which they are derived?

Splice variants are sequences that occur naturally within the cells and tissues of individuals. The physiological activity of splice variant products and the original protein, from which they are varied, may be the same (although perhaps at a different level), opposite, or completely different and unrelated. In addition, variants may have no activity at all.

When a variant and the original sequence have the same or opposite activity, they may differ in various properties not directly connected to biological activity, such as stability, clearance rate, tissue and cellular localization, temporal pattern of expression, up or down regulation mechanisms, and responses to agonists or antagonists.

A certain variant may be expressed mainly in one tissue, while the original sequence from which it has been varied, or another variant derived from the same sequence, may be expressed mainly in another tissue. The presence or level of specific splice variants may be the cause, and/or indicative of, a disease, disorder, pathological or normal condition.

Using well designed DNA chips, as well as other methods, it is possible to determine the differential expression pattern of various variants in various tissues. Understanding of the distribution of splice variants in various tissues is exteramely important for understanding the physiological function of the genes and for developing and targeting pharmaceuticals, as well as for diagnostic purposes.

Splice variants have tremendous impact on drug development and on diagnostic applications

Many more new drug targets, therapeutic protein molecules and diagnostic markers than previously appreciated become available if new splice variants are known.
Since a drug may be effective against one variant but not another, or may cause side effects because it targets all splice variants, an effective drug needs to target the splice variant expressed in the target tissue.
Because soluble variants with therapeutic or disease-related functions may be naturally occurring in specific tissues, they may be outstanding candidates for drug targets or protein therapeutics.
Variants may have no activity at all and may serve as dominant negative natural inhibitors.
New splice variants often offer a strong IP position, even if the previously identified splice variant is patented or is in the public domain. Thus, splice variants may be utilized to generate new proprietary drug targets, protein therapeutics and markers for diagnostics.
The presence or level of specific splice variants may be utilized to diagnose a disease or disorder.

Novel Gene Portfolio

Compugen's 44 functional groups