Rapid antimicrobial susceptibility testing (AST) is a method for quickly determining the most effective antibiotic therapy for patients with bacterial infections. These techniques enable the detection and quantification of antibiotic-resistant and susceptible bacteria metabolites at concentrations near or below ng/mL in complex media. Employing bacterial metabolites as a sensing platform, the system integrates machine learning data analysis processes to differentiate between antibiotic susceptibility and resistance in clinical infections within an hour. With the results, a clinician can prescribe appropriate medicine for the patient's bacterial infection.

Researchers at the University of California, Davis have developed agents made from terpenoids and salicylates that can be used as anesthetics in human and non-human animals, as well as environmentally friendly euthanasia agents in food-producing animals.

BACKGROUND: Triacetic acid lactone (TAL) is an important building block for a diverse set of chemicals and plastic polymers. Native pathways using microbes can serve as an environmentally-friendly and renewable source of TAL production. However, microbial production of TAL is limited to a few platform microbes. Further, native pathways using platform microbes such as E. coli show toxicity to TAL, which reduces its production. Therefore, there is a need for thiolases that provide higher yield and can be used in additional microorganisms. TECHNOLOGY OVERVIEW: Researchers at the Joint BioEnergy Institute (JBEI) have discovered novel thiolases for production of Triacetic acid lactone (TAL) via platform microorganisms. The discovered thiolases achieved production of 2.77 g/L of TAL when expressed in E. coli, which is the highest titer production reported using E. coli. The discovered thiolases were identified from homologs of Cupriavidus necator, and their TAL production was verified by in vitro and in vivo testing. Unlike the energetically expensive native TAL-producing enzyme 2-pyrone synthase, the discovered thiolases utilize acetyl-CoA instead of malonyl-CoA as an extension unit. The Burkholderia thiolases identified by the researchers can be engineered to further boost production of TAL in existing platform microorganisms such as E. coli, as well as other microorganisms such as yeasts. DEVELOPMENT STAGE: Validated system

The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets. The programmable nature of these systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation. There is a need in the art for additional CRISPR-Cas systems with improved cleavage and manipulation under a variety of conditions and ones that are particularly thermostable under those conditions. UCB researchers created a set of efficient CRISPR-Cas9 proteins from a thermostable Cas9 from the thermophilic bacterium Geobacillus stearothermophilus (GeoCas9) through directed evolution. The gene editing activity of the evolved mutant proteins was improved by up to four orders of magnitude compared to the wild-type GeoCas9. The researchers showed that the gene editors based on the evolved GeoCas9 can be effectively assembled into lipid nanoparticles (LNP) for the rapid delivery to different cell lines in vitro as well as different organs or tissues in vivo. The LNP-based delivery strategy could also be extended to other gene editors.  

Researchers at the University of California, Davis have developed a method of treating infections caused by Clostridium perfringens bacteria - via inhibiting the bacteria’s normal quorum sensing processes.

The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation.  There is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).     UC Berkeley researchers discovered a new type of CasPhi/12j protein.  Site-specific binding and/or cleavage of a target nucleic acid (e.g., genomic DNA, ds DNA, RNA, etc.) can occur at locations (e.g., target sequence of a target locus) determined by base-pairing complementarity between the Cas12 guide RNA (the guide sequence of the Cas12 guide RNA) and the target nucleic acid.  Similar to CRISPR Cas9, the compact Cas12 enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.  

Researchers at the University of California, Davis have developed adjunctive therapies applicable to multiple types of infectious conditions. These therapies – derived from compounds found in natural herbs - also have potential prophylactic efficacy.

Researchers at the University of California, Davis have developed a biologic treatment for mitigating pain and treating acute urinary tract infections (UTIs) in canines.

Researchers at the University of California, Davis have developed monoclonal antibodies with multiple applications relevant to canine PD-1 and PD-L1.

Techniques such as genome editing, gene therapy, and CRISPR-based gene expression require robust methods of delivering genetic information. The effectiveness of delivery depends on the amount of DNA or RNA that can be delivered.  In some cases there is a strict upper-limit on the amount of DNA or RNA that can be delivered.  For example, AAV vectors for mammalian gene delivery are limited to genetic cargos of < 5 kb.  In general, and irrespective of the delivery vector, larger DNA constructs are delivered less efficiently and so it is advantageous to use smaller constructs where possible. It is therefore advantageous to compress constructs. Methods of compression that do not require removal of genetic elements (“lossless compression”) are very desirable since size requirements can be met without compromising functionality.     In order to reduce the number of bases (DNA or RNA) required to encode larger constructs, UC Berkeley researchers have developed a method for compressing genetic information.   The method can be applied to two elements which be encoded in the same or different reading and can also be applied to a single genetic elements. 

Mutated versions of Cas12a that remove its non-specific ssDNA cleavage activity without affecting site-specific double-stranded DNA cutting activity. These mutant proteins, in which a short amino acid sequence is deleted or changed, provide improved genome editing tools that will avoid potential off-target editing due to random ssDNA nicking.

The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation.  Current CRISPR Cas technologies are based on systems from cultured bacteria, leaving untapped the vast majority of organisms that have not been isolated.  There is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).     UC Berkeley researchers discovered a new type of Cas 12 protein.  Site-specific binding and/or cleavage of a target nucleic acid (e.g., genomic DNA, ds DNA, RNA, etc.) can occur at locations (e.g., target sequence of a target locus) determined by base-pairing complementarity between the Cas12 guide RNA (the guide sequence of the Cas12 guide RNA) and the target nucleic acid.  Similar to CRISPR Cas9, Cas12 enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.    

Despite many recent improvements in dialysis treatment, End Stage Renal Disease (ESRD) patients on hemodialysis continue to experience an annual mortality rate of approximately 20%, a rate worse than many cancers. Researchers at UCI have identified an association between increased levels of endocannabinoid (EC) in ESRD patients’ serum and decreased risk of death thereby providing a potential therapy to enhance survival times for patients.

Metagenomic analysis of microbial DNA from groundwater samples revealed a new protein, CasX, that prevented bacterial transformation by plasmid DNA when expressed with cognate crRNAs targeting the plasmid8. Sequence analysis of CasXrevealed no similarity to other CRISPR-Cas enzymes, except for the presence of a RuvC nuclease domain similar to that found in both Cas9 and Cas12a enzyme families as well as transposases and recombinases. The evolutionary ambiguity of CasX hinted at a distinct structure and mechanism for DNA targeting, but without reconstitution of a functional CasX enzyme it was not possible to determine its mechanism of plasmid interference.   UC Berkeley inventors found variant CasX polypeptides that induce programmable, site-specific genome repression in E. coli and genome editing in human cells, distinct from Cas9 and Cas12a, which establishes this enzyme family as a third CRISPR-Cas system for genetic manipulation.

Effective and easily accepted system of oral delivery of therapeutic drugs.

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas systems are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation, so there is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).   Researchers have shown that Class 2 CRISPR Cas protein and their variants can be used in a complex for specific binding and cleavage of DNA. The Class 2 CRISPR Cas complex utilizes a novel RNA and a guide RNA to perform double stranded cleavage of DNA and the complex is expected to have a wide variety of applications in genome editing and nucleic acid manipulation. 

Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas systems are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation, so there is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).   UC Berkeley researchers discovered a new type of Cas protein, CasZ.  (CasZ) is short compared to previously identified CRISPR-Cas endonucleases, and thus use of this protein as an alternative provides the advantage that the nucleotide sequence encoding the protein is relatively short.  The researchers have shown that the CRISPR CasZ protein and its variants can be used in a complex for specific binding and cleavage of DNA. The CRISPR CasZ complex utilizes a novel RNA and a guide RNA to perform double stranded cleavage of DNA and the complex is expected to have a wide variety of applications in genome editing and nucleic acid manipulation. 

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas systems are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation, so there is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).   Previously UC Berkeley researchers discovered a new type of Cas protein, CasY (also referred to as Cas 12d protein).  CasY is short compared to previously identified CRISPR-Cas endonucleases, and thus use of this protein as an alternative provides the advantage that the nucleotide sequence encoding the protein is relatively short.  CasY utilizes a guide RNA to perform double stranded cleavage of DNA. The researchers introduced CRISPR-CasY into E. coli, finding that they could block genetic material introduced into the cell.  Further research results indicated that CRISPR-CasY operates in a manner analogous to CRISPR-Cas9, but utilizing an entirely distinct protein architecture containing different catalytic domains.   CasY is also expected to function under different conditions (e.g., temperature) given the environment of the organisms that CasY was expressed in.  Similar to CRISPR Cas9, CasY enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation. Recent studies have shown that the CasY complex utilizes a novel RNA, in addition to the guide RNA, to perform double stranded cleavage of DNA. Similar to CRISPR Cas9, CasY enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.   

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets. The programmable nature of these systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation. There is a need in the art for additional CRISPR-Cas systems with improved cleavage and manipulation under a variety of conditions and ones that are particularly thermostable under those conditions.     UC researchers discovered a new type of RNA-guided endonuclease (GeoCas9) and variants of GeoCas9.  GeoCas9 was found to be stable and enzymatically active in a temperature range of from 15°C to 75°C and has extended lifetime in human plasma.  With evidence that GeoCas9 maintains cleavage activity at mesophilic temperatures, the ability of GeoCas9 to edit mammalian genomes was then assessed.  The researchers found that when comparing the editing efficiency for both GeoCas9 and SpyCas9, similar editing efficiencies by both proteins were observed, demonstrating that GeoCas9 is an effective alternative to SpyCas9 for genome editing in mammalian cells.  Similar to CRISPR-Cas9, GeoCas9 enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.   

Researchers at the University of California, Davis have cultured a titi monkey adenovirus (TMAdV,) and used the virus to develop a model of human respiratory disease.

Researchers at the University of California, Davis have discovered a new signal pathway involved in depression. This could be a potential target of pharmacological treatment of central nervous system disease and specially depression in man and companion animals. The technology could be best practiced with soluble epoxide hydrolase inhibitors, which have high oral bioavailability, good pharmacokinetics, picomolar potency, low toxicity and CNS activity.

Soft-tissue injuries and organ transplantation are common in modern combat scenarios. Organs and tissues harvested for transplantation need to be preserved during transport, which can be very difficult. Micro and nanobubbles (MNBs) offer a new technology that could supply oxygenation to such tissues prior to transplantation, thus affording better recovery and survival of patients. Described here is a novel device capable of producing MNB solutions that can be used to preserve viability and function of such organs/tissue. Additionally, these solutions may be used with negative pressure wound therapy to heal soft-tissue wounds.

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Calibri; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation.  Current CRISPR Cas technologies are based on systems from cultured bacteria, leaving untapped the vast majority of organisms that have not been isolated.  There is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).     UC Berkeley researchers discovered a new type of Cas protein, CasY.  CasY is short compared to previously identified CRISPR-Cas endonucleases, and thus use of this protein as an alternative provides the advantage that the nucleotide sequence encoding the protein is relatively short.  CasY utilizes a guide RNA to perform double stranded cleavage of DNA. The researchers introduced CRISPR-CasY into E. coli, finding that they could block genetic material introduced into the cell.  Further research results indicated that CRISPR-CasY operates in a manner analogous to CRISPR-Cas9, but utilizing an entirely distinct protein architecture containing different catalytic domains.   CasY is also expected to function under different conditions (e.g., temperature) given the environment of the organisms that CasY was expressed in.  Similar to CRISPR Cas9, CasY enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation.   

96 Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:Calibri; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin;} The CRISPR-Cas system is now understood to confer bacteria and archaea with acquired immunity against phage and viruses. CRISPR-Cas systems consist of Cas proteins, which are involved in acquisition, targeting and cleavage of foreign DNA or RNA, and a CRISPR array, which includes direct repeats flanking short spacer sequences that guide Cas proteins to their targets.  Class 2 CRISPR-Cas are streamlined versions in which a single Cas protein bound to RNA is responsible for binding to and cleavage of a targeted sequence. The programmable nature of these minimal systems has facilitated their use as a versatile technology that is revolutionizing the field of genome manipulation.  Current CRISPR Cas technologies are based on systems from cultured bacteria, leaving untapped the vast majority of organisms that have not been isolated.  There is a need in the art for additional Class 2 CRISPR/Cas systems (e.g., Cas protein plus guide RNA combinations).   UC Berkeley researchers discovered a new type of Cas protein, CasX, from groundwater samples. CasX is short compared to previously identified CRISPR-Cas endonucleases, and thus use of this protein as an alternative provides the advantage that the nucleotide sequence encoding the protein is relatively short.  CasX utilizes a tracrRNA and a guide RNA to perform double stranded cleavage of DNA. The researchers introduced CRISPR-CasX into E. coli, finding that they could block genetic material introduced into the cell.  Further research results indicated that CRISPR-CasX operates in a manner analogous to CRISPR-Cas9, but utilizing an entirely distinct protein architecture containing different catalytic domains.   CasX is also expected to function under different conditions (e.g., temperature) given the environment of the organisms that CasX was expressed in.  Similar to CRISPR Cas9, CasX enzymes are expected to have a wide variety of applications in genome editing and nucleic acid manipulation. 

Researchers at the University of California, Davis have developed a method of delivering targeted bioactives that is applicable to the agricultural, food processing, cosmetic, veterinary and medical industries.