Cancer is driven by genetic mutations, notably in TP53, which is altered in ~50% of all cancer cases across various types. In certain cancers such as ovarian, non-small cell lung (NSCLC), and pancreatic cancers, up to 70–90% of cases are found to have TP53 mutations. TP53 mutations also tend to be clonal, arising early and persisting across tumor cells in a heterogenous population. Restoring p53 function for tumor regression has been considered the "holy grail" of cancer therapy. However, no approved therapies are available to target the p53 protein due to its lack of druggable pockets and the difficulty of re-activating defective transcription factors. Conventional treatments like chemotherapy induce systemic DNA damage, leading to widespread side effects.  Therefore, there is a need for compositions and methods that address the above. UC Berkeley researchers and collaborators at Utah State University and the University of Utah have developed methods and compositions for cleaving chromosomal DNA in a eukaryotic cell that address some of the problems with cancer therapies mentioned above.  Such methods generally include contacting a target RNA inside of a eukaryotic cell with a CRISPR complex that includes a Cas12a2 protein and a guide RNA.  The Cas12a2 is programmed to selectively kill cancer cells by targeting cancer-specific transcripts. This approach eliminates cancer cells by inducing trans chromatin cleavage, triggering DNA damage and cell death. Unlike existing methods, RNA-guided Cas12a2 senses cellular RNA signatures to shred chromatin, enabling precise targeting of undruggable mutations. 

Site-selective covalent modification of proteins is key to the development of new biomaterials, therapeutics, and other biological tools. As examples in the biomedical field, these techniques have been applied to the construction of antibody-drug conjugates, bispecific cell engagers, and targeted protein therapies, among other applications. While many bioconjugation strategies, such as azide-alkyne cycloaddition or thiol-maleimide coupling, have become widely adopted, the improvement of existing techniques is a highly active area of chemical biology research, as is the development of new synthetic applications of these methods. Key focuses of such efforts include increasing reaction efficiency and ease, balancing selectivity with tag size, and expanding the modification options beyond traditional cysteine and lysine residues. UC Berkeley researchers have developed compounds and methods using tyrosinase to couple small-molecule dithiols to tyrosine-tagged proteins, which effectively introduces a free thiol handle and provides a convenient method to bypass genetic incorporation of cysteine residues for bioconjugation. These newly thiolated proteins were then coupled to maleimide probes as well as other tyrosine-tagged proteins. The researchers were also able to conjugate targeting proteins to drugs, fluorescent probes, and therapeutic enzymes. This easy method to convert accessible tyrosine residues on proteins to thiol tags extends the use of tyrosinase-mediated oxidative coupling to a broader range of protein substrates. 

Achieving durable engraftment and spatial localization of engineered microbes in complex environments, such as the gut microbiome, has been a persistent challenge. Current methods to select and isolate engineered microbes in the lab rely on antibiotic-based selection systems, which are unsuitable for in vivo applications due to safety concerns, environmental risks, and regulatory hurdles. Moreover, these methods lack the precision needed for selective recovery and targeting within diverse microbial communities.  UC Berkeley researchers have developed an innovative framework that integrates plasmid-based systems and CRISPR-associated transposase systems (CASTs) to enable precise delivery of genetic cargoes encoding surface display systems. These systems, when expressed, allow engineered microbes to display modular binding domains capable of interacting with a range of targets, including but not limited to host associated mucus and magnetic particles. This modularity expands the toolkit for selective enrichment, spatial targeting, and functionalization of engineered microbes in diverse contexts. For example, modified microbes can be magnetized for recovery through magnetic separation or equipped with binding domains to interact with other substrates or biomolecules, unlocking targeted applications in microbiome engineering, therapeutic delivery, and biomanufacturing. This approach not only enables the enrichment and spatial targeting of engineered microbes within complex communities, such as those in the gut, but also provides a versatile method for isolating bacterial strains or directing microbes to specific niches without relying on antibiotics. By combining plasmid modularity with the precision and stability of CASTs, the platform establishes a robust and adaptable solution for microbiome modulation. 

      Raman spectroscopy, the inelastic scattering of light off molecular vibrations or solid- state phonons, is a critical method in chemical analytics, biological imaging, and materials or even art characterization. A common method for signal enhancement is surface enhanced Raman spectroscopy (SERS), where noble metal or dielectric nanostructures locally enhance the incoming and/or scattered field. SERS has found wide-spread applications in bio- analytics, fundamental science, viral and bacterial classification, and the study of tissue samples. Yet, obstacles towards more wide-spread adoption with wider scope are poor SERS substrate reproducibility and local hotspot fluctuations of metallic SERS substrates, and background emission from molecules, analytes, hot electrons, plasmons, or carriers in dielectrics that can significantly interfere with small signals of target analytes in SERS.       UC Berkeley researchers have developed an improved method for SERS that simultaneously minimizes spurious background emission, minimizes local heating even under high excitation powers, and maximizes the Raman signal enhancement of dielectric SERS substrates. Together these advantages render the method a powerful contender for sought after quantitative SERS and reliable analyte and single- molecule detection without fluctuations or other perturbations from SERS substrates. This enables commercially relevant usage, particularly in the biosciences and diagnostics, DNA/RNA sequencing, protein sequencing, determination of biomolecular binding constants, interconversion kinetics between biomolecular conformers, post-translational modifications, determination of molecular folding statuses, and classification of different proteoforms. It further has commercial potential in environmental monitoring, food safety, semiconductor inspection, polymer quality control and research, quality control in pharmaceuticals – including vesicles for drug delivery-, materials science, and physical science research.

      Optical tweezers generated with light modulation devices have great importance for highly precise laser imaging and addressing systems e.g. excitation and readout of single atoms, imaging of interactions between molecules, or highly precise spatial trapping and movement of particles. To generate dynamic optical tweezers adjustable at the microsecond scale, acousto-optic deflectors (AOD) are commonly used to modulate the spatial profile of laser light. Dynamic optical tweezers are increasingly relevant for emerging technologies such as neutral atom quantum computers, and tightly focused laser spot arrays may enable advanced imaging and/or semiconductor processing applications. However, dynamic optical tweezer systems capable of rapid, aberration-free movement of one or multiple atoms in independent, arbitrary three-dimensional trajectories with minimal aberration have not yet been realized.      UC Berkeley researchers have developed a dynamic optical tweezer system that overcomes significant defects such as limited 2D motion and optical aberration present in existing art. Carefully designed waveform modulation of one or more acousto-optic deflector lenses (AODLs) enables atomic addressing and rapid tweezer motions while minimizing significant optical aberrations present in prior methods. The invention is capable of microsecond scale single or multi tweezer motion in arbitrary three-dimensional trajectories without the use of translation stages. The invention can flexibly address one atom, multiple atoms, or the entire array.

Most tumors are extremely complex, having many oncogene drivers and are, therefore, not as amenable to a CRISPR-mediated therapies. Pediatric low-grade glioma (pLGG) is a type of brain cancer that arises during childhood. Some interventions exist, including surgery and inhibitor drugs, but there is no cure for pLGG. In contrast to most types of cancer (which feature a host of driver oncogenes), pLGG tumors tend to arise due to a single driver oncogene mutation. This aspect makes pLGG a potential target for a genome editing intervention. Because CRISPR enzymes can precisely discriminate between wild-type and mutant sequences in a single cell, enzymes such as Cas9 can target a mutant oncogene site without impacting the corresponding wild-type locus in a non-cancer cell. UC Berkeley researchers have developed a CRISPR-based strategies for anti-cancer genome editing.  The invention consists of a suite of genome editing strategies with the capacity to selectively inactivate the oncogene underlying tumor pathology, for example, mutations in pLGG. Deployed via a delivery strategy with the capacity for broad genome editing of brain cells, our strategy will have the capacity to halt – and potentially reverse – tumor growth.

This invention is a portable retinal imaging device that images the fundus of the eye by coupling an ocular imaging device with a mobile device. It features ocular lenses, filters, a fixation display, and a light source for preview and image capture, with application programming on the mobile device controlling gaze and stitching images for a wider field of view.

Ribosomes, traditionally known for catalyzing amide bond formation, have been found to also promote reactions involving various non-canonical amino acids, alpha-hydroxy acids, and certain beta-hydroxy/amino acids. This document describes a new discovery: peptides containing a dehydrolactic acid motif can rapidly isomerize to a backbone-embedded α,γ-diketoamide via a spontaneous O to C acyl shift. This reaction introduces a newly formed backbone C–C bond as a ketone, addressing a long-standing challenge in generating internal C–C bonds within genetically encoded polypeptides.