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Richmond Hill, Canada

Carmi S.,Bar - Ilan University | Borukhov I.,Compugen | Levanon E.Y.,Bar - Ilan University
PLoS Genetics | Year: 2011

Adenosine-to-inosine modification of RNA molecules (A-to-I RNA editing) is an important mechanism that increases transciptome diversity. It occurs when a genomically encoded adenosine (A) is converted to an inosine (I) by ADAR proteins. Sequencing reactions read inosine as guanosine (G); therefore, current methods to detect A-to-I editing sites align RNA sequences to their corresponding DNA regions and identify A-to-G mismatches. However, such methods perform poorly on RNAs that underwent extensive editing ("ultra"-editing), as the large number of mismatches obscures the genomic origin of these RNAs. Therefore, only a few anecdotal ultra-edited RNAs have been discovered so far. Here we introduce and apply a novel computational method to identify ultra-edited RNAs. We detected 760 ESTs containing 15,646 editing sites (more than 20 sites per EST, on average), of which 13,668 are novel. Ultra-edited RNAs exhibit the known sequence motif of ADARs and tend to localize in sense strand Alu elements. Compared to sites of mild editing, ultra-editing occurs primarily in Alu-rich regions, where potential base pairing with neighboring, inverted Alus creates particularly long double-stranded RNA structures. Ultra-editing sites are underrepresented in old Alu subfamilies, tend to be non-conserved, and avoid exons, suggesting that ultra-editing is usually deleterious. A possible biological function of ultra-editing could be mediated by non-canonical splicing and cleavage of the RNA near the editing sites. © 2011 Carmi et al.


Kliger Y.,Compugen
Biopolymers | Year: 2010

The development of peptides with therapeutic activities can be based on naturally occurring peptides or alternatively on de novo design. The discovery of natural peptides is often a matter of serendipity. In part, this is because natural peptides are typically proteolytically cleaved out from precursor proteins, a feature that averts the direct benefits of the genomic revolution. The first part of this review describes attempts to create a more systematic identification of natural peptides relying on a two step process. In the initial step, an in silico peptidome is predicted through the use of machine learning. Then, various computational biology tools are tailored to focus on peptides predicted to have the desired biological activity; for example, activating a GPCR or modulating the cellular arm of the immune system. The second part of the review is devoted to de novo peptide design and focuses on arguably the simplest scenario in which the designed peptide corresponds to a contiguous protein subsequence. Amongst these peptides, those corresponding to helical segments are prominent, mainly due to their relative ability to fold independently. Inspired by the clinical success of viral entry inhibitors, which are peptides corresponding to helical segments in viral envelope proteins, a computational tool for the identification of intramolecular helix-helix interactions was developed. Using this approach, peptides having anti-cancer, anti-angiogenic, and anti-inflammatory activities have been recently rationally designed and biologically characterized. 2010 Wiley Periodicals, Inc.


Disclosed are peptide ligands for G-protein coupled receptors that are useful for treating disorders associated with G-protein coupled receptor activation.


This invention relates to a novel target for production of immune and non-immune based therapeutics and for disease diagnosis. More particularly, the invention provides therapeutic antibodies against VSIG1, ILDR1, LOC253012, AI216611, C1ORF32 or FXYD3 antigens, which are predicted co-stimulatory family members and which are differentially expressed in cancers including, lung cancer, ovarian cancer, and colon cancer, and diagnostic and therapeutic usages. The use of these antibodies for modulating B7 costimulation and related therapies such as the treatment of autoimmunity are also provided. This invention further relates to the discovery of extracellular domains of VSIG1 and its variants, FXYD3 and its variants, ILDR1 and its variants, LOC253012 and its variants, AI216611 and its variants, and C1ORF32 and its variants which are suitable targets for immunotherapy, cancer therapy, and drug development.


This invention relates to a novel target for production of immune and non-immune based therapeutics and for disease diagnosis. More particularly, the invention provides therapeutic antibodies against VSIG1, ILDR1, LOC253012, AI216611, C1ORF32 or FXYD3 antigens, which are predicted co-stimulatory family members and which are differentially expressed in cancers including, lung cancer, ovarian cancer, and colon cancer, and diagnostic and therapeutic usages. The use of these antibodies for modulating B7 costimulation and related therapies such as the treatment of autoimmunity are also provided. This invention further relates to the discovery of extracellular domains of VSIG1 and its variants, FXYD3 and its variants, ILDR1 and its variants, LOC253012 and its variants, AI216611 and its variants, and C1ORF32 and its variants awhich are suitable targets for immunotherapy, cancer therapy, and drug development.

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