256 innovations from Bar-Ilan University, available for licensing, co-investment, or spin-out through BIRAD.
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.
Teman Adam
Dynamic memory topology, layout and full array that can be manufactured in a standard FinFET (digital) process with low area, low power consumption, and high bandwidth
Yehoshua Yaron
The current research deals with the development of an innovative technology for the future food industry, by growing different types of microalgae in unique hydrogel capsules made of polyvinyl alcohol/polyvinyl pyrrolidone/alginate (PVA/PVP/A)). The macrocapsules will serve as a basis to produce cultured seafood. These algae-based macrocapsules will be used as food supplements rich in nutrients, and as food for humans and other animals such as fish, poultry, etc. In this work, these unique hydrogel macrocapsules were developed and their composition and structure were optimized, and the ability to grow algae in them was demonstrated. The technologies that currently exist for growing algae are based on growing in a medium, in plates, and artificially in reactors, encountering many difficulties stemming, among other things, from various bacterial and fungal infections. In addition, to ensure adequate growth, an increased amount of expensive growth medium is used. As part of the present work, an innovative and unique technology for growing algae was developed instead of the technologies that exist today. We introduce microalgae plus growth mediums into macrocapsules that have been uniquely developed by algae encapsulation processes during the preparation of the hydrogel macrocapsules. The confinement of the algae is done to provide them with a place to grow and to protect the algae cells from infections and harmful microorganisms. We also provide microalgae the conditions they need for their growth: light, temperature, and growth medium. The capsules may also contain fragrances, flavors and chosen color. The monitoring of the growth of the microalgae was carried out in two main ways: 1. Tracking the intensity of the color of the macrocapsules, which increases as the concentration of algae in the macrocapsules increasing, 2. Monitoring the concentration of chlorophyll (absorbance at 680 nm) which increases as the concentration of algae in the macrocapsules increasing. It was most clearly demonstrated that the growth of the microalgae entrapped in the macrocapsules is significantly faster than their growth in the conventional methods. The capsules could be used as a basis for various food products by combining them as a raw material or as "ink" for 3D printing. In growing algae with the proposed technology, there is a significant saving in water growing areas compared to the technologies that exist today. The proposed technology of enclosing the algae in capsules will reduce the cases of pollution and at the same time reduce the amount of expensive medium required to grow the cells. This will reduce the growing expenses and make it possible to create future food at a cheaper price. Also, we save on the growing costs of the stage of separating the algae from the water, which is an expensive stage that requires resources and consumes a lot of energy. Furthermore, the capsule shell itself is used as a protein substitute and edible. In addition, if necessary, the separation of the cultured algae from the hydrogel polymeric macrocapsules can easily be achieved by adding chelating metal ions such as EDTA or sodium citrate. in conclusion, the use of the aforementioned macrocapsules will enable a controlled and clean process in a configuration close to the final food product, resulting in significant cost savings.
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.
Cohen Cyrille
In this invention, we have identified a gene involved in amino acid metabolism that when over-expressed in primary human lymphocytes, enhances T-cell function
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.
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.
Mandel Yossi
A device and system for storing and maintaining the viability of an enucleated eye globe ex vivo. The device includes a part-spherical eye bed designed to support the globe and integrate with a perfusion system for nutrient and oxygen delivery. Retinal functionality is monitored using electrophysiology by recording electroretinogram (ERG) signals, providing a robust measure of tissue viability and preservation quality for preclinical testing or potential transplantation.
Noked Malachi
Spherical LiNiO2 (LNO) is synthesized by scalable solid state route. Strategically controllable synthesis approach endowed with suppression of detrimental phase transformation. The presented approach facilitate dense LNO with controllable shape and in-situ doping option.
Yeshurun Yossi
Full details available on request
Tischler Yaakov Raphael
The invention is an unmanned aerial vehicle (UAV) platform physically and optically linked to a remote base station via a flexible, high-bandwidth optical fiber tether. The architecture decouples the heavy, high-cost, and environmentally sensitive components of a spectroscopic system (such as high-power pulsed/tunable laser engines, complex modulation optics, and laboratory-grade spectrographs or gas-phase analysis hardware) from the mobile flight platform. The flexible tether is optimized for advanced optical transport, supporting single-fiber configurations (utilizing co-axial transceiver optics or double-clad fibers to route both excitation and collection paths through a single line) or multi-fiber bundles (separating excitation and collection lines). To eliminate fiber-induced background noise and accommodate ultra-fast pulses, the system incorporates hollow-core photonic crystal fibers (HC-PCFs), or alternatively utilizes standard, cost-effective solid silica fibers combined with an on-board micro-optical filtering payload head on the UAV. This payload head incorporates high-performance laser cleanup bandpass filters that actively strip away fiber-induced silica Raman sideband spectral peaks and autofluorescence before the excitation light hits the target, alongside longpass/notch/shortpass edge filters that isolate the target's weak spectroscopic signals from backscattered pump light. The UAV payload head features a dynamically adjustable optical delivery system capable of switching between a tightly focused beam configuration (for high-power density point-and-shoot spectroscopy like spontaneous/resonance Raman or LIBS) and a collimated beam configuration (for wide-area illumination, plume absorption, or thermal-ignition mitigation of sensitive energetics). Additionally, the drone features an extractive sampling configuration containing an enclosed internal gas cell for high-precision Cavity Ring-Down Spectroscopy (CRDS) or Tunable Diode Laser Absorption Spectroscopy (TDLAS). To operate in intense ambient-light environments (such as bright daylight) without blinding the spectrometer, the system incorporates distributed optical and electronic noise-suppression packages. These include: An excitation/collection package using ultra-fast time-gating to physically slice out daylight; A spectral-modulation package utilizing Shifted Excitation Raman Difference Spectroscopy (SERDS) under both continuous-wave and pulsed regimes to mathematically subtract invariant background light; and A payload-filtering package on the UAV utilizing tunable Fabry-Pérot etalons or narrow-band collection filters to isolate the signal before it propagates down the return line. The system also supports hybrid photo-acoustic and laser Doppler vibrometry (LDV) tracking, using phase-locked lock-in demodulation distributed on-board or down-fiber to isolate target signatures from UAV motor and rotor noises.
