This technology represents a pioneering approach to vaccine development, focusing on encapsulated adjuvants and antigens to enhance efficacy while minimizing side effects.

A cutting-edge vaccine delivery platform that enhances tumor treatment by co-delivering MHC class I and II restricted antigens.

A revolutionary vaccine platform enabling the co-delivery of multiple toll-like receptor agonists and an antigen for potent immune responses.

Efficient delivery and expression of exogenous proteins in cell populations (e.g., cells in the body) for gene therapy / gene editing applications, is an important goal in biomedicine. This can be hampered by inefficient transport of enzymes from outside the body to cells within the body. When delivering nucleic acids or proteins of interest (e.g., DNA editing enzymes), most delivery methods can only reach and enter a small subset of cells within a tissue. There is a need for compositions and methods for improved delivery of proteins of interest, and such is provided herein. UC Berkeley researchers have discovered that delivery of a molecular cargo to a target cell can be more efficiently achieved by using a cell as the delivery vehicle. This can be accomplished by delivering a nucleic acid encoding an enveloped delivery vehicle (EDV) (one that comprises a molecular cargo), to a producer cell where the producer cell produces the EDV and thereby delivers the molecular cargo to neighboring cells (referred to herein as receiver cells). Thus, there is no human intervention between delivery of a subject nucleic acid (encoding the EDV) and subsequent delivery of EDVs to target cells (receiver cells).  

Researchers at UCI have discovered the tertiary structure of the Chlamydia major outer membrane protein (MOMP). Despite historical challenges in formulating an effective vaccine, recent advancements in understanding MOMP's structure offer new pathways for vaccine development against urogenital and ocular infections caused by C. trachomatis.

Influenza A virus (IAV) poses an ever-evolving threat due to its high mutation rate and ability to reassort, leading to new viral variants that evade existing vaccines and treatments. Historically responsible for devastating global pandemics, including the infamous Spanish Flu, and currently fueling concerns with the spread of highly pathogenic Avian Influenza (HPAI H5N1), IAV remains a pressing global health challenge.UC Berkeley researchers have developed an Antisense Oligonucleotides (ASO) therapy that is an next-gen approach to combating influenza by modulating IAV activity at its genetic level. Unlike traditional antivirals or seasonal vaccines that struggle to keep up with mutating strains, this ASOs therapy targets the ultra-conserved U12 region within the IAV RNA genome, offering broad-spectrum efficacy against even the most elusive influenza strains.  

This technology introduces a novel vaccine delivery system using thermosensitive hydrogels for sustained antigen release, aiming to improve immune response durability and breadth.

Researchers at the University of California, Davis have developed advanced compounds targeting neuraminidase activity to combat viral infections and understand cellular mechanisms.

Brief description not available

Researchers at the University of California, Davis have developed an approach to elicit powerful immune responses by engineering the binding capabilities of single chain trimer (SCT) proteins to CD8.

Researchers from UC San Diego developed an invention that enables protein expression to be upregulated using specific proteins and/or peptide sequences derived from SARS-CoV-2 proteins that are engineered to recognize specific mRNA transcripts by fusion to RNA-targeting modules such as CRISPR/Cas systems. They anticipate that these proteins can be fused or tethered to any engineered RNA-targeting moiety/module such as PUF/Pum, and pentatricopeptide proteins.

α-Fetoprotein (AFP) is a fetal glycoprotein produced by the majority of human hepatocellular carcinoma tumors and other tumor types. Delineating differences between fetal 'normal' AFP (nAFP) and tumor-derived AFP (tAFP), investigators at UCSF and the Parker Institute for Cancer Immunotherapy have uncovered a novel role for tAFP in altering metabolism via lipid-binding partners. They have developed a pharmaceutical composition comprising AFP bound by a fatty acid which, depending on the fatty acid used, can have an immunosuppressive effect allowing for the treatment of inflammatory diseases.  AFP bound to other fatty acids can eliminate the immune suppressive impact and have a neutral effect which allows for the development of dendritic cell (DC) vaccines presenting AFP epitopes which could be used to treat and prevent tumor AFP-expressing cancers.  

Poly (ethylene glycol) (PEG) is a widely used polymer in a variety of consumer products and in medicine. PEG is viewed as being well-tolerated, but previous studies have identified anti-PEG antibodies and pseudoallergic reactions in certain individuals. The increased use of lipid nanoparticles (LNPs) as contrast agents or in drug delivery, along with the introduction of mRNA vaccines encapsulated in PEGylated lipid nanoparticles is a concern.  UC Berkeley researchers have created Lipid nanoparticles with new polymers that do not generate PEG antibodies. Cell and animal work demonstrate that these new polymers deliver mRNA efficiently in vitro and in vivo.

Researchers at UC Irvine have identified and tested a molecular target that regulates T cell function during chronic viral infection and cancer. The molecular target is one of the high mobility group proteins (HMGB2). HMGB2 is a DNA binding protein that regulates transcriptional processes, meaning that its modulation will have profound effects on T cell differentiation and ultimate function by altering the expression of many genes.

Cationic, ionizable lipids are a type of lipid that can switch between neutral and positive charges depending on the pH of their environment. They're crucial in lipid nanoparticle (LNP) formulations, particularly for RNA delivery, where they play a key role in encapsulating and releasing the RNA payload. Unfortunately, conventional chemical de novo synthesis of cationic and ionizable lipids is slow, expensive and inefficient. UC Berkeley researchers have developed compositions and methods of synthesizing cationic, ionizable lipids via standard solid phase peptide synthesis protocols, and integration of (i) the solid phase lipid synthesis, (ii) initial cell screening, and (iii) animal organ or cell targeting in an automated robotic system (ARS).

Vaccine design is at the forefront of therapeutic development. Candidate proteins for recombinant vaccine design are expressed as soluble proteins lacking the native transmembrane domain. These proteins are often fused with multimerization domains to stabilize the native oligomeric state of the candidate protein. However, these multimerization domains can elicit off-target immune responses, raising concerns regarding risks of unintended immunogenicity. Thus, there is a need to eliminate potential off-target effects of recombinant vaccine candidates that contain multimerization domains such as the foldon domain.

Researchers at the University of California, Davis have developed a method to stop bacterial growth while maintaining desirable metabolic functions for therapeutic and biotechnological applications.

The inventors have developed an engineering approach to identify novel and nonobvious membrane-associated accessory protein (MAAP) sequence variants that confer increased Adeno-associated virus (AAV) secretion during packaging. The technique is based upon the iterative process of sequence diversification and selection of functional gene variants known as directed evolution. First, the inventors generated a library of more than 1E6 MAAP variants. The variants were subjected to five rounds of packaging into an AAV2 capsid for which MAAP expression was inactivated without altering the viral protein VP1 open reading frame (ORF) (AAV2-MAAP-null). Among each iterative packaging round, the inventors observed a progressive increase in both the overall titer and ratio of secreted vector genomes conferred by the bulk selected MAAP library population. Next-generation sequencing uncovered common mutational features that were enriched up to over 10,000-fold on the amino acid level. Individual MAAP variants were isolated and systematically tested for effect on recombinant AAV2-MAAP-null packaging in HEK293 cells. The inventors predict that this work may be applicable to increasing per-cell AAV output in industrial settings, potentially reducing global costs and increasing functional vector recovery in downstream manufacturing processes.BACKGROUNDParvoviruses are small, single-stranded DNA viruses that are ubiquitously found in many animal species. AAV is a prototypic dependoparvovirus whose replication cycle requires the function of helper genes from larger co-infected viruses such as Adenoviruses or Herpesviruses. The natural genome of AAV contains ~4.7 kb of ssDNA that encodes up to ten known proteins in a highly overlapped fashion. The rep gene encodes four protein products named based on their molecular weight: Rep72 and Rep68 facilitate genomic replication, whereas Rep52, and Rep40 play essential roles in loading nascent ssDNA genomes into assembled capsids. Downstream of rep lies the cap gene, which encodes three known protein products off of overlapping reading frames: VP1, VP2, and VP3 are structural proteins that assemble to form the capsid, the assembly activating protein (AAP) targets VP proteins to the nucleus and is involved in capsid assembly. The most recently discovered AAV-encoded gene is the membrane-associated accessory protein (MAAP). MAAP is encoded by an alternative ORF in the AAV cap gene that is found in all presently reported natural serotypes. Gene delivery by recombinant AAV (rAAV) have shown significant success in both research and clinical gene therapy applications. In the rAAV system, Rep and Cap are removed from between AAV’s 5’ and 3’ inverted terminal repeats (ITRs) and provided in trans. Instead, a transgene of interest is inserted between the ITRs and subsequently packaged into the nascent AAV capsids. However, manufacturing quantities of good manufacturing practice (GMP)-grade rAAVs necessary to achieve current and projected dosing requirements–particularly in a clinical context–presents a significant hurdle to expanding rAAV-based gene therapies. Recently, evidence has emerged supporting a functional role of MAAP in AAV egress. This led to the hypothesis that MAAP could be engineered to facilitate increased levels of secreted AAV produced from HEK293 cells. 

The inventors present a novel strategy for achieving pathogen opportunistic pathogenesis, with broad implications for treating infectious diseases. In a comprehensive analysis of Kaposi sarcoma associated herpesvirus (KSHV), a medically important virus, the inventors discovered novel antiviral targets and gene function, and identified opportunistic factors with dual functions of regulating both the immune environment/responses and viral reactivation/replication. This discovery includes:A collection of KSHV mutants with inactivation or deletion of each of the 91 predicted open reading frames (91 mutant strains). Methods and reagents (e.g. primers) for construction of the collection of KSHV mutants. The identity of 44 KSHV essential genes, which represent potential antiviral targets (including 27 newly identified essential genes). Methods for construction of gene-inactivation and rescued mutants, and for tagging and introducing foreign genes into the KSHV genome. These approaches can be used for vector and vaccine development. Growth properties of viral mutants with inactivation of non-essential genes.Methods for screening mutants in different human cell lines.Opportunistic factors of KSHV and all other animal viruses that have dual functions as both the modulators of immune environment/response and regulators of viral reactivation/replication.   

The inventors demonstrate that polyethylene glycol (PEG) conjugated to cholesterol via an acid degradable linkage composed of an azide-benzaldehyde acetal has the potential to allow solid lipid nanoparticles (SLNs) to be PEGylated with mole ratios up to 50%. The azide-benzaldehyde acetal, has its azide in the para position, and generates stable acetals with a t ½ of > 1000 minutes at pH 7.4. These PEG-acetals can be formulated into SLNs, and stored, and then reduced prior to biological use, to generate an amino acetal that has t ½ < 60 minutes at pH 7.4 and several minutes at pH 5.0. The ultra-PEGylated lipids were efficient at transfecting a variety of organs, including the muscle, the lung, spleen and liver and were also able to transfect the blood. Acid degradable PEG-lipids have great potential for overcoming the PEG dilemma, but have previously been challenging to develop due to the synthetic challenges associated with working with acetals and their instability at pH 7.4. (SLNs contain a PEGylated lipid, generally in the 1-5% range, which is needed to maintain SLN stability, size, and tissue diffusion, and lower toxicity. However, excessive PEGylation also results in lower cell uptake and endosomal disruption — a paradox referred to as the PEG dilemma.) The inventors anticipate numerous applications of the azide-benzaldehyde acetal linker, given its unique ability to be stable prior to reductive activation. 

Following the pandemic, there is a clear need for improved technology in the area of vaccines. A pressing challenge is to enable a rapid response to emerging threats, using an established platform technology.

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Researchers at the University of California, Davis have developed a more cost effective and consistent method for producing capsular polysaccharides, a component of certain types of vaccines.

Researchers at UC Berkeley have developed methods to probe the conformational landscape of the SARS-CoV-2 Spike protein in the prefusion and ligand binding variations. The Spike protein from SARS-CoV-2 is the primary target for current vaccines against COVID-19 and is the focus of many therapeutic efforts. This large, heavily glycosylated trimeric protein is responsible for mediating cell entry via recognition of host cell receptors. A stabilized prefusion version of the structure of the Spike protein (termed S-2P) has been widely used for vaccine development and many structure/function studies, which have demonstrated that like other class 1 viral fusion proteins, the SARS-CoV-2 Spike protein is dynamic and samples several different conformations during its functional lifecycle. However, there are few experimental studies on the dynamics within the pre-fusion state of the SARS-CoV-2 Spike protein. The protein’s conformational landscape and the effects of perturbations, such as ligand binding (including receptor and antibody binding) or amino acid substitutions in emerging variants of concerns, are unknown. Stage of Research The inventors have developed hydrogen-deuterium exchange monitored by mass spectrometry (HDX-MS) methods to probe the conformational landscape of the soluble spike prefusion ectodomain, as well as the effects of ligand binding and sequence variation. They uncovered a stable alternative conformation that interconverts slowly with the canonical prefusion structure. This conformation is an open trimer, with easily accessible RBDs that expose the S2 trimer interface, providing new epitopes in a highly conserved region of the protein.

Streptococcus pyogenes (group A Streptococcus [GAS]) is a leading health and economic burden worldwide, with an estimated 700 million infections occurring annually. Among these are 18.1 million severe cases that result in over 500,000 deaths. Despite active research, a protective vaccine remains elusive, leaving antimicrobial agents as the sole pharmacological intervention against GAS. To date, penicillin remains a primary drug of choice for combating GAS infections. However, despite no apparent emergence of resistant isolates, the rate of treatment failures with penicillin has increased to nearly 40% in certain regions of the world. Due to the high prevalence of GAS infection and the decreasing efficacy of the available repertoire of countermeasures, it is critical to investigate alternative approaches against GAS infection. An emerging strategy for combating pathogenic bacteria involves targeting virulence. To avoid immune clearance, GAS expresses a wide variety of secreted and cell-associated virulence factors to facilitate survival during infection. Despite decades of inquiry into the role and regulation of GAS virulence factors, the function and potential importance of many proteins involved in pathogenicity remain unknown.