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A Protein Inhibitor Of Cas9

  Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 nucleases, when complexed with a guide RNA, effect genome editing in a sequence-specific manner. RNA-guided Cas9 has proven to be a versatile tool for genome engineering in multiple cell types and organisms.  There is a need in the art for additional compositions and methods for controlling genome editing activity of CRISPR/Cas9.   UC Berkeley researchers have discovered a new protein that is able to inhibit the Cas9 protein from Staphyloccocus aureus (SauCas9). SauCas9 is smaller than the frequently used Cas9 from Streptococcus pyogenes, which has a number of benefits for delivery. The inhibitor is a small protein from a phage and is capable of strongly inhibiting gene editing in human cells.

Topical Anti-proliferative Agents for Melanoma

Due to the year-to-year increase in skin cancer incidences and dramatic decrease in survival, once the melanoma has metastasized, a preventative treatment for skin cancer would be significant. Currently, the only defenses against melanoma are applying sun protection factor (SPF) regularly and protecting oneself from direct sun exposure. In a 2015 national survey conducted by the Center for Disease Control and Prevention (CDC), 34% of adults reported using SPF 15 or higher and 35% of adults reported having a sunburn in the past year.    UC Berkeley researchers have discovered active antiproliferative compounds that can be applied post-sunburn to prevent the growth and metastases of melanoma and therefore, could reduce the number of melanoma incidences per year. Based on preliminary data, they are developing a compound cocktail composed of active lead compounds to develop an anti-proliferative and cytostatic topical treatment of melanoma to slow down tumor development. 

Cas12-mediated DNA Detection Reporter Molecules

Class 2 CRISPR-Cas systems are streamlined versions in which a single Cas protein (an effector protein, e.g., a type V Cas effector protein such as Cpf1) bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that continues to revolutionize the field of genome manipulation.    Cas12 is an RNA-guided protein that binds and cuts any matching DNA sequence. Binding of the Cas12-CRISPR RNA (crRNA) complex to a matching single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA) molecule activates the protein to non-specifically degrade any ssDNA in trans. Cas12a-dependent target binding can be coupled to a reporter molecule to provide a direct readout for DNA detection within a sample.  UC Berkeley researchers have developed compositions, systems, and kits having labeled single stranded reporter DNA molecules that provide a sensitive readout for detection of a target DNA. 

CasX Nickase Designs, Tans Cleavage Designs & Structure

Metagenomic analysis of microbial DNA from groundwater samples revealed a new protein, CasX, that prevented bacterial transformation by plasmid DNA when expressed with cognate crRNAs targeting the plasmid8. Sequence analysis of CasXrevealed no similarity to other CRISPR-Cas enzymes, except for the presence of a RuvC nuclease domain similar to that found in both Cas9 and Cas12a enzyme families as well as transposases and recombinases. The evolutionary ambiguity of CasX hinted at a distinct structure and mechanism for DNA targeting, but without reconstitution of a functional CasX enzyme it was not possible to determine its mechanism of plasmid interference.   UC Berkeley inventors found variant CasX polypeptides that induce programmable, site-specific genome repression in E. coli and genome editing in human cells, distinct from Cas9 and Cas12a, which establishes this enzyme family as a third CRISPR-Cas system for genetic manipulation.

Selective Nitrogen Adsorption Using a Vanadium Metal-Organic Framework

Natural gas, composed primarily of methane, has many potential uses as a cleaner and more renewable source of energy than other fossil fuels. However, about 20% of US natural gas reserves contain levels of N2 that are too high for pipeline processing. Using natural gas from renewable sources also encounters this problem. Furthermore, in processing steps to create high-purity methane from its various sources, the removal of N2 remains a significant energetic cost. This separation is typically performed through cryogenic distillation, and improvements in energy efficiency of this separation are necessary to utilize the many available sources of methane. Switching to membrane or adsorbent-based technologies could potentially alleviate this challenge. Size selective molecular sieves and membranes have demonstrated some ability for separating N2 from CH4, but face problems with scalability and selectivity; and current adsorbents need significant improvements in selectivity and capacity for N2 to be commercially viable.  To address this situation, researchers at UC Berkeley have developed a new adsorbent V2Cl2(btdd) with exceptional affinity for nitrogen, such that early experiments already demonstrate a N2/CH4 selectivity of over 10x greater than any reported material. The Berkeley material is a permanently porous vanadium(II)-containing metal-organic framework (MOF). It represents the first example of a MOF with five-coordinate vanadium(II) centers as the primary metal node. The electronic properties of these five-coordinate V(II) centers make this MOF uniquely reactive towards relatively inert and weak electron acceptors, such as nitrogen, creating a stronger M–N2 interaction than any known MOF. Additionally, the high-density of V(II) centers translates to a high gas uptake capacity, qualifying this material as a promising N2/CH4 selective adsorbant. Key performance parameters can be tuned as the building blocks are synthetically modifiable.

Dynamic Statistical Contingency Fuel

Airlines rely on flight dispatchers to perform the duty of fuel planning. In addition to required fuel loading categories, flight dispatchers also uplift contingency fuel to be on the aircraft to hedge against various uncertainties (e.g. weather uncertainty, traffic congestion uncertainty, air traffic control uncertainty etc.) to ensure flight safety and reduce the risk of diversions. To provide consistent and objective fuel planning, some airline Flight Planning System (FPS) provides recommended contingency fuel numbers for dispatchers based on a statistical analysis of historical fuel consumption for similar flights. This recommended contingency fuel is called statistical contingency fuel (SCF). However, due to limitations of the current SCF estimation approach, the application of SCF is limited. Researchers at the University of California, Berkeley have developed a novel methodology based on quantile regression models to overcome the limitations of the current SCF estimation approach. The proposed method takes various factors such as weather, aircraft type, airport, and historical operational conditions into account so that SCF can be estimated in a dynamic, flexible, and more accurate way. Their results have shown that dynamic SCF performs much better than the current SCF estimated by airline FPS and also more sensitive to the specific conditions faced by a given flight. SCF calculated using this novel method will be higher under adverse weather conditions, whereas the current method for determining SCF does not take these conditions into account. The result of using this novel SCF is expected to reduce fuel loading, since dispatchers typically ignore SCF based on the current method when conditions are poor, instead simply loading a very large amount of contingency fuel. By reducing fuel loading, not only would a plan be able to take off sooner, but this would also result in reduced fuel consumption as the aircraft’s weight would be reduced.

New Method For Underwater Wireless Communication

Underwater communication presents many challenges in order to transmit data with large bandwidth and over long distance and/or over a wide area.  Indeed, water absorption, scattering and turbidity prevent radio waves to be used similarly as in air. Acoustic transmission has therefore been the standard technology for decades, but suffers from a very small bandwidth (less than 1 Mbps), whereas a video stream or conventional large data stream requires a bandwidth higher than 10Mbps.  Free Space Optical systems have been developed and tested underwater lately taking advantage of the development of lasers and LEDS with wavelengths around 500nm. In this range, water absorption is minimal and optical communication range could theoretically reach 150m with a bandwidth in the tens of Mbps. Large distance communication and correct alignment between the transmitter and the receiver remain however challenging.   UC Berkeley researchers have developed a new method for long-distance and/or wide­area underwater wireless communication using Autonomous Underwater Vehicles (AUVs) equipped with a Free Space Optical system allowing high bandwidth communication. The high stability and agility of the AUV allows to maintain a correct alignment between the receiver and the transmitter of two different AUVs keeping the data communication operational. 

Micro-Optical Tandem Luminescent Solar Concentrator

Silicon photovoltaic (“Si-PV”) modules currently dominate the solar energy market. Increased progress into Si-PV efficiency enhancements combined with historically low module costs aim to decrease the overall Levelized Cost of Electricity (“LCOE”) to a point competitive with non-renewable energy sources. Despite recent LCOE reductions, Si-PV technology remains economically inferior to fossil fuels. Additionally, flat-plate Si solar modules generally require geographical locations with high direct normal incidence (“DNI”) sunlight conditions in order to maintain module performance. Both the strict DNI requirement and the high LCOE of Si-PV cells ultimately limit the dissemination of solar power into the global energy market. A solution for the capturing of diffuse sunlight includes the use of optical concentrators.  One class of optical concentrators includes luminescent solar concentrators (“LSCs”).  Luminescent solar concentrators have garnered interest due to their ability to utilize diffuse light and their potential for use in architectural applications such as large area power-generating windows. However, LSCs have not yet reached commercialization for photovoltaic power generation, largely due to their comparatively low power conversion efficiencies (“PCEs”) and lack of scalability.     Researchers at UC Berkeley and other educational institutions have developed luminescent solar concentrators that  can be designed to minimize photon thermalization losses and incomplete light trapping using various novel components and techniques.