This invention introduces a novel approach to cardiac tissue stimulation and maturation through the use of photoactive organic and biological material blends.

Researchers at the University of California, Davis have developed technology that provides an advanced system for monitoring and supporting patient resuscitation and mechanical ventilation, enhancing clinical decision-making.

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 Traditional gRNA design tools have relied on static libraries with limited genome annotations and outdated scoring methods, lacking the flexibility to incorporate context-specific genomic information.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 transgenic zebrafish model enabling controlled pancreatic β-cell ablation to simulate chronic hyperglycemia and study diabetes-related pathology.

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.

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.