Researchers at the University of California, Davis have developed advanced epigenetic methods and systems that detect and assess developmental risks in embryos caused by maternal stress prior to conception.

Monitoring of viral infections such as with the SARS-CoV-2 virus was vital to detection and characterization of new variants before they became widespread and allowed public health agencies to deploy resources and develop policies in advance of new waves of the virus. I The ARTIC Network developed a panel of primers and a workflow for whole genome sequencing of SARS-CoV-2 using multiplex PCR. This became a popular strategy for sequencing. The ARTIC protocol generates overlapping PCR amplicons that span the SARS-CoV-2 genome using a defined multiplex PCR primer set. These were sequenced and mapped to the SARS-CoV-2 genome to generate a high quality consensus sequence of the variant in the sample. While ARTIC was developed for SARS-CoV-2, the protocol is readily adaptable to a wide array of viruses. Despite its clear utility, challenges arose for ARTIC: new variants would arise that the consensus primers would not recognize and all testing for those new variants would be compromised. Normalization of samples with high variation of starting template proved difficult and sequencing library preparation was not optimized for convenience, speed, or cost.  

A highly precise and efficient gene-editing tool designed to correct single-nucleotide DNA mutations responsible for genetic diseases.

Researchers at the University of California, Davis have enabled the creation of hybrid crops with enhanced fertility and yield by overcoming genetic distance barriers.

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Researchers at the University of California, Davis have developed a scalable, plant-based method using somatic embryogenesis to produce high yields of water-soluble melanin externally from walnut tissues.

Together with Researchers at the University of Texas at Austin, researchers at the University of California, Davis have developed a method for synthesizing long polynucleotides using scaffolded cooperative binding and enzymatic ligation to improve yield, modification compatibility, and assembly accuracy.

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Researchers at the University of California, Davis have developed alacto-oligosaccharide (GOS) formulations selectively promote growth of beneficial Bifidobacteria species by tailoring oligosaccharide chain lengths.

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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 diagnostic screen using DNA methylation and genetic variant analysis from newborn blood spots that enables early prediction of autism spectrum disorder (ASD) risk.

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.

Researchers at the University of California, Davis have developed novel antisense oligonucleotide (ASO) therapies that enhance ADNP protein expression to address haploinsufficiency in ADNP syndrome.

Researchers at the University of California, Davis have developed a computer-implemented method to identify viral mutations that enhance transmission and predict their prevalence in populations over time.

The Major Histocompatibility Complex (MHC), is a genomic region that expresses proteins involved in immune system functions and that are important for organ transplantation. In humans, this type of gene is referred to as the Human Leukocyte Antigen (HLA). The HLA region is haplotypic, with all of the region inherited from one parent. HLA is highly polymorphic within the human population, both in terms of protein structure as well as genomic variability.This high genomic diversity makes accurate genotyping difficult using methods such as short-read sequencing. That said, current long-read sequencing methods and analysis can yield incomplete and inaccurate results. 

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.

Professor Linlin Zhao and their team from the University of California, Riverside have developed mTAP, a new chemical probe engineered to selectively bind to abasic sites within mitochondrial DNA without affecting nuclear DNA. Unlike non-specific agents, mTAP is equipped with a mitochondria-targeting group, ensuring its precise localization. This invention is advantageous over current technology because its mechanism of action involves forming a stable chemical bond with damaged DNA sites, thereby protecting mtDNA from enzymatic cleavage and maintaining its replication and transcriptional activities.    Fig 1: The UCR mitochondria-targeting water-soluble probe mTAP exclusively reacts with mitochondrial abasic sites, and retains mitochondrial DNA levels under genotoxic stress which are responsible for certain mitochondrial diseases. 

In eukaryotic cells, DNA is packaged into chromatin, a dynamic structure that can shift between more open (euchromatin) and condensed (heterochromatin) states to regulate processes like gene expression, DNA repair, and genome organization. This regulation is controlled by chromatin regulators, i.e. proteins that add, remove, or interpret epigenetic modifications, as well as remodel chromatin structure, working alongside transcription factors. These mechanisms are highly conserved across diverse eukaryotic species, underscoring their fundamental biological importance. However, experimentally testing the full function of these proteins remains challenging. Current high-throughput approaches often rely on protein fragments rather than full-length chromatin regulators, which can miss key functional domains and enzymatic activities. Additionally, most chromatin engineering has been developed in a few model systems, creating a need for more versatile tools that can function across a broader range of organisms, including plants and other less-studied eukaryotes. This invention comprises a chromatin regulator protein fused to a DNA-binding protein that in turn modifies gene transcription. The inventors used a multi-kingdom, full length chromatin regulator (CR) library to uncover several potent chromatin regulator proteins. These proteins include the human proteins SAP25, MBD3, RCOR1, MTA2, WDR82, DPY30, the plant proteins CMT3, SWC2, or the yeast proteins CHZ1, IES5, and TTI1 respectively. These proteins are then fused to DNA binding proteins with the product of that fusion being referred to as CR fusion proteins. These CR fusion proteins are then able to proteins to increase or decrease transcription of specific genes in eukaryotic cells when introduced to cells with specific nucleic acids.

The enzyme Rubisco, largely found in plants, algae, and photosynthetic bacteria, is responsible for the majority of biological carbon fixation on Earth. However, it has slow kinetics and has resisted decades of protein engineering efforts to improve its catalytic rate. UC Berkeley researchers have designed an in-vivo system that allows large libraries of Rubisco sequences to be functionally screened for improved enzymatic properties. They generated an E. coli strain whose growth rate is linked to Rubisco performance, allowing for pooled assays and the use of deep sequencing as a readout. This system allows for much higher throughput screening of Rubisco than any previous method and significantly increases opportunities to identify catalytically superior Rubisco sequences. 

CRISPR-derived nucleases offer unprecedented precision and ease of use for targeting specific genomic sites. However, the efficient delivery of gene editing tools into plant cells remains a significant hurdle. Current methods rely on a laborious and time-consuming tissue culture pipeline and can induce undesirable changes to the genome and epigenome. To circumvent these limitations, one alternative is to use plant viral vectors for the delivery of compact gene editors and their guide RNA (gRNA). UC Berkeley and UC Davis inventors found that the use of tobacco rattle virus (TRV) vectors to deliver reRNA and variant TnpB proteins to plants results in surprisingly high efficiencies of genome editing not only in the infiltrated cells, but also systemically (e.g., seeds and non-infiltrated leaves). Delivery via TRV caused systemic viral spread into the shoot apical and floral meristematic regions, leading to unexpectedly high efficiencies of genome editing in non-infiltrated cells (i.e., spread of genome editing), for example, surprisingly high efficiencies of genome editing in non-infiltrated systemic leaves as well as in the germline (e.g., seeds).