Class 2 CRISPR-Cas are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. Theprogrammable nature of these minimal systems has facilitated their use as a versatile technology for genome editing.  CRISPR-Cas enzymes with reduced requirements for a protospacer-adjacent motif (PAM) sequence adjacent to the target site could improve the breadth of target sites available for genome editing.  UC Berkeley researchers have developed a novel PAM-loose 12a variants, nucleic acids encoding the variant Cas12a proteins and systems using these variants that make the Cas12a-based CRISPR technology much easier to design a DNA target for carrying out genome editing in human cells. 

mRNA-based cancer therapies include vaccination via mRNA delivery of tumor neoantigens, delivery of mRNA encoding for immune checkpoint and other protein therapeutics, and induced expression of anticancer surface proteins such as CAR expression in T cells. Success requires transfection of a critical number of immune cells together with appropriate immune-stimulation to effectively drive anti-tumor responses. UC Berkeley researchers have developed an adjuvant-assisted mRNA LNP delivery method that uses mRNA LNP and adjuvant to enhance delivery of nucleic acids to immune cells in vivo and stimulate immune cells. They demonstrated the use of this system to reduce mRNA reporter protein expression in the liver and enhance protein expression in the spleen in mice and also demonstrated this system can be used to genetically engineer T cells by delivering a Cre-recombinase mRNA construct- transfection and editing of approximately 4% of T cells is achieved in vivo. The immune response is superior in our system compared to current, commercial lipid nanoparticle delivery technologies.

TnpB protein has generated interest as a potential compact genome-editing tool, due to the short amino acid sequence (408 AAs for ISDra2 TnpB), which overlaps with the wRNA sequence in their genomes of origin. There is a need for compositions and methods that provide more efficient TnpB systems. UC Berkeley researchers have created variant TnpB proteins and variant wRNAs that increase cleavage activity and/or DNA binding activity (e.g., revealed as endonuclease activity such as on-target endonuclease activity). These variant TnpB proteins include an amino acid sequence having one or more amino acid substitutions relative to a corresponding wild type TnpB protein. Also provided are variant TnpB wRNAs that can form a complex with a TnpB protein and a second nucleotide sequence that can hybridize to a target sequence of a target nucleic acid, thereby guiding the complex to the target sequence.

Brief description not available

Brief description not available

Researchers from UC San Diego developed a patent-pending novel Synthesis of Virtual Array Manifold (SVAM) sensing approach for the mmWave single RF chain systems. More specifically, this new technology for sensing leads to faster and more robust beam alignment. UCSD believes this contribution will have significant impact on the traditional paradigm for sensing in mmWave systems.

Researchers at the University of California, Davis have developed an algorithm for designing and identifying complex structures having custom release profiles for controlled drug delivery.

Antibodies against poly(ethylene glycol) (PEG) have the potential to cripple the development of lipid nanoparticle (LNP) based therapeutics and new polymers that can stabilize LNPs are greatly needed. Developing alternatives to the PEG-lipid has been challenging partially because of the synthetic challenges associated with making PEG-lipids.  UC Berkeley researcher have created methods for synthesizing PEG replacement polymers based on RAFT block copolymerization and have shown that the block co-polymers synthesized via RAFT polymerization can replace the PEG on LNPs and can generate LNPs that are more efficient at delivering mRNA than PEG-LNPs and are less immunogenic. Block copolymers synthesized via RAFT have great potential for improving the performance of LNPs given their ability to be rapidly synthesized, the commercial availability of numerous methacrylate monomers and the large functional group tolerance of RAFT.