Brief description not available

Brief description not available

Brief description not available

UC Berkeley researchers have developed a sophisticated computer-implemented framework that leverages transformer architectures to model the evolution of biological sequences over time. Unlike traditional phylogenetic models that often assume sites evolve independently, this framework utilizes a coupled encoder-decoder transformer to parameterize the conditional probability of a target sequence given multiple unaligned sequences. By capturing complex interactions and dependencies across different sites within a protein or genomic sequence, the model estimates the transition likelihood for each position. This estimation allows for a high-fidelity simulation of evolutionary trajectories. This approach enables a deeper understanding of how proteins change across different timescales and environmental pressures.

Researchers at the University of California, Davis have developed a nanoparticle system combining photothermal therapy and chemotherapy for enhanced cancer treatment.

Researchers at the University of California, Davis have developed a technology that introduces an approach to creating semi-living, non-replicating cellular systems for advanced therapeutic applications.

Clustered regularly interspaced short palindromic repeats (CRISPR) screening is a cornerstone of functional genomics, enabling genome-wide knockout studies to identify genes involved in specific cellular processes or disease pathways. The success of CRISPR screens depends critically on the design of effective guide RNA (gRNA) libraries that maximize on-target activity while minimizing off-target effects. Current CRISPR screening lacks tools that can natively integrate next-generation sequencing (NGS) data for context-specific gRNA design, despite the wealth of genomic and transcriptomic information available from modern sequencing approaches. Traditional gRNA design tools have relied on static libraries with limited genome annotations and outdated scoring methods, lacking the flexibility to incorporate context-specific genomic information. Off-target effects are also a concern, with CRISPR-Cas9 systems tolerating up to three mismatches between single guide RNA (sgRNA) and genomic DNA, potentially leading to unintended mutations that could disrupt essential genes and compromise genomic integrity. Additionally, standard CRISPR library preparation methods can introduce bias through PCR amplification and cloning steps, resulting in non-uniform gRNA representation.

A revolutionary drug modality for the selective modification and degradation of intracellular proteins in lysosomes.

A cornerstone of bacterial molecular biology is the ability to genetically manipulate the microbe under study. Manipulating the genomes of bacteria is critical to many fields. Such manipulations are made by genetic engineering, which often requires new pieces of DNA to be added to the genome. It is often difficult to move genes into a recalcitrant destination organism due to surveillance systems (CRISPR, Restriction Modification) of the destination/host which degrade invading DNA . It may be commercially desirable to evade these systems in the destination organism. However, evading these systems may require significant experimental effort to design and implement.

A groundbreaking method for the efficient isolation and preservation of high-purity small extracellular vesicles (sEVs - exosomes) from biofluids using a novel EXO-PEG-TR reagent.

BMSO represents a groundbreaking advancement in crosslinking mass spectrometry (XL-MS), enabling comprehensive mapping of protein-protein interactions.

Researchers at the University of California, Davis have developed a novel cell segmentation technology for accurate analysis of non-spherical cells and that offers a comprehensive, high-throughput approach for analyzing the transcriptomic and metabolomic data to study complex biological processes at the single-cell level.

This technology offers a groundbreaking approach to map biomolecules in 3D space with subcellular resolution, revolutionizing our understanding of tissue organization and disease propagation.

      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.

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.

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.

Developing structurally complex peptide macrocycles is a critical strategy for addressing "undruggable" protein-protein interactions. To expand the chemical space available for drug discovery, UC Berkeley researchers have developed a versatile synthesis method that embeds quinoline and other heterocycles directly into the macrocyclic backbone. The approach utilizes substituted 2-aminocarbonyl co-substrates to produce peptide hybrids featuring biaryl atropisomeric axes. These axes provide a unique form of axial chirality that can be engineered to be either conformationally mobile or stable, allowing for the precise three-dimensional "locking" of the peptide into a target-optimal shape. By integrating these rigid pharmacophores, the resulting macrocycles achieve enhanced topological diversity and superior binding affinity compared to traditional cyclic peptides.

Targeted protein degradation represents a transformative approach in drug discovery by using small molecules to hijack the cell's natural disposal machinery. In this advancement, UC Berkeley researchers have engineered a vinylsulfonyl covalent handle designed for the rational construction of monovalent degraders. Unlike traditional bivalent degraders (PROTACs), which can be large and difficult to deliver into cells, these monovalent molecules are more compact and specifically target a cysteine residue within DCAF16, a substrate receptor of the CUL4-DDB1 E3 ubiquitin ligase. By covalently "gluing" the target protein to DCAF16, the system triggers the ubiquitination and subsequent proteasomal destruction of disease-causing proteins.

An innovative sulfoxide-containing MS-cleavable cross-linker, DBrASO, specifically designed for cysteine residues and aimed at enhancing protein-protein interactions studies and protein complexes architecture analysis.

An innovative mass spectrometry platform that utilizes sulfoxide-containing MS-cleavable heterobifunctional photoactivated cross-linkers to enhance protein structural elucidation.

Transcription factors are critical regulators of gene expression, but they have long been considered "undruggable" due to their lack of deep, well-defined binding pockets and their high degree of intrinsic disorder. To overcome this, UC Berkeley researchers have developed a new class of covalent monovalent degraders that utilize chemoproteomic platforms to target and eliminate these proteins. Unlike traditional inhibitors that must compete with natural ligands for a binding site, these compounds form a permanent covalent bond with specific, often disordered cysteine residues on the target transcription factor. This interaction induces structural destabilization of the protein, triggering its recognition and subsequent destruction by the cell's ubiquitin-proteasome system. This platform has already successfully produced potent degraders for major oncogenic drivers such as $\beta$-catenin (CTNNB1), MYC, and the androgen receptor variant AR-V7.

The efficient delivery of protein-based therapeutics into the cytosol is a significant hurdle in drug development, as most internalized proteins remain trapped and degraded within endosomal compartments. To address this challenge, UC Berkeley researchers have identified a set of biophysical "design rules" that promote the successful escape of proteins from these vesicles. The researchers found that selecting or engineering proteins with high intrinsic disorder or a specific thermal stability (T_m)—specifically the tendency to unfold at physiological temperatures—greatly enhances their ability to penetrate the endosomal membrane. This discovery provides a rational engineering framework for creating next-generation intracellular biologics, including enzymes and gene-editing tools, that can effectively reach their target sites within the cell.

Researchers at UC Berkeley have developed methods to deliver biomolecules to plant cells using new plant-derived cell penetrating peptides (CPPs). Despite the revolution in DNA editing that the last decade has brought, plant genetic engineering has not been able to benefit to the same extent. This is due to certain challenges in plant physiology that limit the delivery of exogenous protein cargos, as required in the CRISPR-Cas9 system, primarily due to the plant cell wall. In mammalian cells, for instance, cargo delivery can be accomplished using cell-penetrating peptides (CPPs) which are short peptides that facilitate the transport of cargo molecules through the plasma membrane to the cytosol. While this technology has been optimized in mammalian cells, few have studied the delivery of CPPs in plants to verify whether the cell wall is permissible to these materials. Another barrier to the use of nanotechnologies for plant biomolecule delivery is the lack of quantitative validation of successful intracellular protein delivery. The near universal dependence on confocal microscopy to validate delivery of fluorescent proxy cargoes can be inappropriate for use in plants due to various physiological plant properties, for example intrinsic autofluorescence of plant tissues. Therefore, there exists an unmet need for new materials and methods to deliver biomolecules to plant cells and to confirm the delivery of proteins of varying sizes into walled plant tissues. Stage of Research The inventors have developed methods to deliver proteins into plant cells using cell penetrating peptides which are appropriate for use with CRISPR-Cas9 technology, siRNAs, zinc-finger nucleases, TALENs, and other DNA editing methods. They have also developed a biomolecule fluorophore-based assay to accurately quantitate protein delivery to plants cells.Stage of DevelopmentResearch - in vitro 

Many genomes encode Restriction-Modification systems (RMs) that act to protect the host cell from invading DNA by cutting at specific sites (frequently short 4-6 base reverse complement palindromes). RMs also protect host DNA from unfavorably being cut by modifying sites within the host DNA that could be targets by the host’s own surveillance enzymes. It is also not unusual to find that these enzymes are adjacent to each other in the host genome. Traditional approaches to understanding these sites involve finding a methylase that is typically adjacent to a restriction enzyme, and then extracting DNA, expressing protein and then testing DNA sequence for evidence of cutting. In certain laboratory research (e.g., programs that involve transforming DNA/RNA) it may be desirable to more comprehensively understand the sequences being surveilled by the host. Moreover, it may be desirable in certain laboratory research to know/predict which surveillance enzymes are present in a genome in order to affect cell transformation efficiency through evasion of those sequences.

Biological fluids are complex, with compositions that vary constantly and evade molecular definition. Nevertheless, within these fluids proteins fluctuate, fold, function, and evolve as programmed. Synthetic heteropolymers capable of emulating such interactions would replicate how proteins behave in biological fluids, individually and collectively, leading the way toward synthetic biological fluids. However, while there exist known monomeric sequence requirements, the chemical and sequence characteristics of proteins at the segmental level, rather than the monomeric level, may be the key factor governing how proteins transiently interact with neighboring molecules (and how biological fluids collectively behave). To address this opportunity, UC Berkeley researchers have developed a new process of heteropolymer design for protein stabilization and synthetic mimics of biological fluids. The process leverages chemical characteristics and sequential arrangements along protein chains at the segmental level to design heteropolymer ensembles as mixtures of disordered, partially folded, and folded proteins. In studies, for each heteropolymer ensemble, the level of segmental similarity to that of natural proteins determines its ability to replicate many functions of biological fluids, including: assisting protein folding during translation; preserving the viability of fetal bovine serum without refrigeration; enhancing the thermal stability of proteins; and, behaving like synthetic cytosol under biologically relevant conditions. Molecular studies further translated protein sequence information at the segmental level into intermolecular interactions with a defined range, degree of diversity and temporal and spatial availability.