20 innovations from Bar-Ilan University, available for licensing, co-investment, or spin-out through BIRAD.
Gonen, Nitzan
Males and females differ drastically in many traits including organ development, behaviour, prevalence of diseases and responses to drugs. It is believed that this difference stem from sex chromosome composition (XY/XX) or sex hormones (Testosterone/ Estrogens). It is impossible to distinguish between the two under normal conditions. We have developed a system of mice that enables to segregate between sex chromosomes and sex hormones and hence understand what are the mechanisms leading to sexual dimorphisms between males and females.
Meital Gal Tanamy
Vaccines based on live attenuated viruses are the most effective strategy for controlling infections, since they elicit long-lasting natural and effective immune response, but entail challenges as safety and virulence. Hepatitis C Virus (HCV) is a major global health problem, causing liver diseases and liver cancer, with millions infected each year and hundreds of thousands of annual fatalities; but no vaccine is currently available for the virus. Here we present a novel computational approach for the accurate predication of virus attenuation. The approach is based on a rational design of weakened virus variants by insertion of high number of synonymous mutations to disrupt the viral RNA’s secondary structure and regulatory sequences important for the viral life cycle. By measuring RNA levels and virus spread in HCV infection model, we showed that these variants have lower viral fitness relative to the wild-type virus, with gradient of attenuation in concordance with the prediction model. Deep sequencing of replicating viruses demonstrated genomic stability of the attenuated variant. Differential expression analysis and evaluation of cancer-related phenotypes revealed that the variants have a lower pathogenic influence on the host cells, compared to the WT virus. These rationally designed variants may be further considered as a promising direction for a viable HCV vaccine. Importantly, the computational approach described here is based on the most fundamental viral regulatory motifs and therefore may be applied for almost all viruses as a new strategy for vaccine development.
Gerber Doron
The invention is a 2-module platform featuring a multi-well plate system for single biological unit isolation and expansion and a nano-volume bioreactor chip that can accurately predict large-scale antibody/protein production.
Albeck Amnon
development of protein-protein interaction inhibitors, whose activity is calcium concentration dependent. Thus, at low calcium conc. the inhibitors will be active (preventing the interaction between the two proteins), but at high concentration they will not interfere with the biological activity.
Piran Ron
The progressive loss of insulin-producing β-cells is central to the pathogenesis of all diabetes types, yet strategies for their regeneration remain limited. Here, we describe the successful implementation of a mathematical prediction we developed: inhibition of somatostatin (Sst) expression enabled robust, glucose-responsive β-cell regeneration and restored insulin independence in diabetic models. Genetic Sst knock out (SstKO) mice spontaneously recovered from chemically induced diabetes. We then rediscovered Cysteamine (Cys), an FDA-approved drug, as a pharmacological inhibitor of Sst production in mouse and human primary islets. Mechanistically, Sst suppression released a brake on intrinsic regenerative pathways within the islet. In diabetic wild-type mice, Cys reproduced the regenerative phenotype of SstKO animals. Importantly, in autoimmune-prone NOD mice, Cys treatment restored β-cell function and insulin independence. Together, these findings identify Sst inhibition as both a regenerative and therapeutic axis for β-cell regeneration, and nominate Cys as a safe, clinically translatable candidate for diabetes therapy
Shokhen Michael
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Ayal Hendel
We have developed a machine learning based approach for analysing treatment vs control multiplexing-PCR and Next-generation sequencing data to infer and quantify CRISPR genome editing off-target activity. Our methods are now well developed and we are in the final stages of writing a full manuscript. The main contributions of this project are the tool and the statistical modelling approach behind it, which lead to improved performance as we demonstrate. Moreover - we observed that using this type of data also allows us to infer translocation/fusion adverse events. These are not addressed by any of the existing approaches (e.g CRISPResso (1 and 2) and ampliCan). We apply our inference methods to experimental data (5 different on-target loci, in different technical configurations and with a total of 230 off-target sites examined) and demonstrate unique findings that also shed a light on translocation mechanisms related to CRISPR genome editing.
Levanon Erez
Recent findings suggest that ICIs fail to invoke an immune response when the tumors lack potent immunogenic peptides called “neoantigens”. The majority of mutations in cancer result in only slightly modified peptides that are unlikely to serve as neoantigens and trigger an immune response – despite checkpoint inhibitor treatment. To overcome this limitation, we developed a computational framework that aids the design of synthetic polymers, called antisense oligonucleotides (ASOs), that manipulate the splicing process in tumor cells to offset protein synthesis machinery and force production of entirely new peptides. Smart, computationally driven, choices of potential targets, will result in highly immunogenic peptides. We expect the combination of our technology with current checkpoint inhibitors, to offer a new and effective strategy in cancer therapy.
Major Dan Thomas
This invention relates to an integrated computational platform — EnzyDock-RxnNet — that combines automated reaction-network enumeration (RxnNet) with mechanistic molecular docking (EnzyDock) to predict, rank, and rationally engineer the product selectivity and promiscuity of terpene synthase enzymes. The platform operates on a quantum-chemistry foundation, parametrizes reactive carbocation intermediates automatically, and scales to full biosynthetic reaction networks encompassing hundreds of intermediates.
Gonen, Nitzan
We have generated testis organoids from embryonic and neonatal mouse testicular cells. We use transwell inserts and well defined media for this. The organoids can be maintained for 9 weeks in vitro and preserve all main testicular cell types. They also display gene expression profiles that are highly similar to the real testis as well as spatial organisation that resemble the testis. We also developed 2 defined media compositions that enable to support the immature versus mature testis states.
Louzoun Yoram
We have developed a novel machine learning for microbiome based classification. The method is based on the translation of samples into images and applying CNN to these images
Qvit Nir
Protein-protein interactions (PPIs) play a key role in a variety of critical biological processes and are involved in many human diseases, including cardiovascular diseases (CVDs), making them attractive therapeutic targets. Peptides have emerged as a promising strategy for targeting PPIs due to their higher specificity compared to small molecules and more rapid clearance than antibodies. Recently, mitochondrial dysfunction has been recognized as a major pathogenic mechanism underlying numerous diseases, including CVDs. Optic atrophy 1 (Opa1), a mitochondrial dynamin-like GTPase, and PTEN-induced kinase 1 (Pink1) are central regulators of mitochondrial quality control and homeostasis. Dysregulation of the Opa1/Pink1 interaction pathway has been associated with impaired mitochondrial function and cellular damage. To further investigate the significance of Opa1/Pink1 PPI in mitochondrial quality and function, we: (1) developed a library of peptides and identified CVP-026, which targets the Opa1/Pink1 PPI; (2) demonstrated that the peptide is selective for the Opa1/Pink1 interaction; and (3) showed that CVP-026 exerts cardioprotective effects in cardiomyocytes and (4) demonstrated protective effects in myocardial infarction (MI) animal models. Taken together, our findings suggest that CVP-026 may represent a promising lead compound for the treatment of diseases associated with mitochondrial dysfunction.
