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. 

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).

Nucleic acid therapies hold vast therapeutic potential. FDA approved therapies include mRNA vaccines against SARS-COV2 and CRISPR/CAS9 treatment to treat sickle cell.  Both therapies use non-viral methods to deliver designer nucleic acid therapies to cells. However, a limitation of these approaches is the lack of organ and cell-specific delivery. Controlling gene delivery and expression in various cell subsets is challenging. UC Berkeley researchers have shown that the nanoscale topology of CpG oligodeoxynucleotide (CpG-ODN) motifs can be used to stimulate various immune cell subsets and alter gene expression from exogenously delivered mRNA in distinct immune cell subsets. CpG-ODNs of different classes are known to induce different inflammatory profiles in immune cells based on the structure and nanoscale topology of the short DNA strand. The researchers have found novel nanostructures which can be used to present or deliver CpGs to various cell subsets and regulate gene expression in these subsets.

Achieving precise and tunable control over endogenous gene expression in eukaryotic cells remains a significant challenge, particularly for therapeutic applications or detailed biological studies where fine-tuning is required rather than complete on/off switching. This innovation, developed by UC Berkeley researchers, addresses this by providing a novel, programmable method for transcriptional tuning. The innovation is a two-domain fusion protein comprising the transcriptional repression domain (TRD) of the methyl-CpG-binding domain (MBD) protein MeCP2 linked to a dead Cas9 (dCas9) domain. When combined with a single guide RNA (sgRNA) that targets a specific endogenous gene, this fusion protein partially inhibits, or "tunes," the expression of that gene. Unlike traditional methods like RNAi or full CRISPR interference (CRISPRi), which often aim for complete knockdown, this system offers a highly specific and titratable way to dial down gene expression, providing a distinct advantage in studies requiring subtle modulation of gene dosage or for developing dose-dependent therapeutic strategies.

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.