25 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.
Fischer Bilha
The detection of subcellular domains in cells can be obtained by specific fluorescent markers. Here we report the use of styryl quinolinium dyes that selectively stain ribosomal RNA (rRNA) in nucleoli and in the cytoplasm of mammalian cells. Specifically, we synthesized a series of 1-methyl-4-(substituted) styryl-quinolinium derivatives, 12a–l. We developed highly efficient microwave-assisted synthesis which prevents the formation of side products, leading to the products in yields greater than 90%. Compounds 12c-f and 12i in various solvents exhibited maximum absorbance at 500–660 nm, molar extinction coefficient of 25400–49000 M
Ayal Hendel
The invention utilizes CRISPR-Cas9 editing and rAAV6 vectors for transgene delivery to correct the RAG1 and RAG2 coding exon. The novelty is in the construct we use for the correction which replaces the entire open reading from of the gene as oposed to standard practice which is to insert the transgene.
Danielli Amos
The invention significantly accelerate the detection time of specific DNA sequences in solution.
Shokhen Michael
I will provide some attached with this document
Piran Ron
Latent autoimmune diabetes in adults (LADA) is a relatively new defined diabetes type. It has a strong autoimmune component, making it similar to type I diabetes (T1D), while its onset is at a later age (30’s or older), making it similar to type II diabetes (T2D). It is still unclear how prevalent LADA is in the general population, as most LADA patients are erroneously diagnosed with T2D receiving imprecise treatment. It is estimated that most lean T2D patients are LADA patients. Therefore, it is estimated that the percentage of LADA patients out of the T2D patients is 10%. Considering that T2D is 90% of all diabetic patients and that T1D is about 8%, making LADA more abundant than T1D (10*90/100=9% of total diabetic patients). All diabetes types eventually end in pancreatic β-cell loss and thus results in the loss of insulin secretion, which causes overproduction and a decreased cellular uptake of glucose. Therefore, developing novel strategies aiming to protect, regenerate, and restore β-cells would represent a promising therapeutic alternative for all patients with diabetes. Researches have identified several drugs which possibly stimulate β-cell proliferation and enhance their function. Among these are γ-Aminobutyric acid (GABA), dipeptidyl peptidase IV inhibitors (DPP-4i) such as Sitagliptin (SIT), or proton pump inhibitors (PPI) like Omeprazole (OMP). We found that the combined treatment (CT) administration demonstrated a significant improvement in diabetic symptoms compared to untreated mice and mice that received GABA, GABA+SIT, GABA+OMP, or SIT+OMP. Moreover, ~30% of the mice that were given CT were COMPLETELY CURED of diabetes and showed normoglycemia for 7 weeks after the last drug administration, an unprecedented achievement for this irreversible disease. We have clear indications that similar success rates also recapitulate in human LADA patients. The challenge was to differentiate the 30% cured from CT unresponsive mice. Thus, we repeated the CT experiment, this time taking blood samples from all mice after diabetes onset but before starting treatment. After the experiment, we returned to the blood samples and arranged them according to the cured/unresponsive. We identified circulating RNA markers that predict 100% response to CT, enabling the successful identification of candidates for CT.
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.
Barda-saad Mira
The immune system employs intricate regulatory mechanisms to ensure that immune cells distinguish foreign invaders from healthy tissues via the ‘education’ process. Natural Killer (NK) cell education is of crucial interest due to its upcoming role in adaptive immunity. In individuals, 13%±6% of the NK cells do not express classical inhibitory receptors as killing inhibitory receptors (KIRs) superfamily and NKG2A. These dysfunctional cells, termed ‘anergic’ NK cells, have relatively lowered cytotoxic potential and reduced pro-inflammatory cytokine secretion. Most research has focused on the role of NK cell education, but the molecular framework underlying NK cell anergy or hypo-responsiveness phenotype remains unknown. Re-programming these cells and enhancing their functional role has great potential for cancer immunotherapy. Here we decipher the underlying molecular mechanism and identify key intrinsic regulators such as EGR2 and DGKα governing NK cell anergy. Together, reinforced by transcriptome analysis, we profile the anergic vs. responsive signature. Furthermore, we demonstrate that silencing these intrinsic regulators revokes NK functionality (cytotoxicity) , thus serving as markers for anergy or hypo-responsiveness and acting as a potential target to reverse dormancy. This newfound approach to “reprogram” them in situ via intrinsic regulators is of high clinical relevance for future NK anti-tumor immunotherapeutic approaches.
Ayal Hendel
Tumor-Infiltrating Lymphocyte (TIL) therapy has emerged as an effective personalized treatment for advanced melanoma. However, several obstacles hinder its optimal implementation in clinical practice. The advent of CRISPR gene editing presents a promising avenue for enhancing TIL therapy by improving the ability of lymphocytes to target tumors more effectively. By making precise modifications to immune cells, it is possible to boost significantly their efficacy in combating cancer. Specifically, the simultaneous targeting of CBL-B and CBL immune checkpoints in CRISPR-modified TILs has demonstrated increased production of cytotoxic molecules and cytokines, thereby enhancing their capability to eradicate cancer cells directly. This innovative approach has the potential to lead to improved clinical outcomes for a broader range of patients with melanoma.
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
Cohen Cyrille
In this invention, we have identified several genes that are part of the glucose metabolism that when expressed in primary human lymphocytes, enhance T-cell function
