A5039567184- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Immunotherapy and Immune Responses
- RNA Interference and Gene Delivery
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Inflammasome and immune disorders
- Immune Cell Function and Interaction
- RNA modifications and cancer
- Antimicrobial Peptides and Activities
- interferon and immune responses
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Thermal Regulation in Medicine
- Cancer-related gene regulation
- Molecular Biology Techniques and Applications
- Virus-based gene therapy research
- Mosquito-borne diseases and control
- Immune cells in cancer
Stanford University
2019-2020
In vitro transcription (IVT) of mRNA is a versatile platform for broad range biotechnological applications. Its rapid, scalable, and cost-effective production makes it compelling choice the development mRNA-based cancer therapies vaccines against infectious diseases. The impurities generated during can potentially impact safety efficacy therapeutics, but their structural complexity has not been investigated in detail yet. This study pioneers comprehensive profiling IVT impurities,...
Myeloid cells play critical and diverse roles in mammalian physiology, including tissue development repair, innate defense against pathogens, generation of adaptive immunity. As that show prolonged recruitment to sites injury or pathology, myeloid represent therapeutic targets for a broad range diseases. However, few approaches have been developed gene editing these cell types, likely owing their sensitivity foreign genetic material virus-based manipulation. Here we describe optimized...
Adenosine-to-inosine RNA editing is catalyzed by adenosine deaminase acting on (ADAR) enzymes that deaminate to inosine. Although many sites are known, few trans regulators have been identified. We perform BioID followed mass spectrometry identify of ADAR1 and ADAR2 in HeLa M17 neuroblastoma cells. known novel ADAR-interacting proteins. Using ENCODE data, we validate characterize a subset the interactors as global or site-specific regulators. Our set includes all four members...
Adenosine-to-inosine RNA editing, catalyzed by adenosine deaminase acting on (ADAR) enzymes, alters sequences from those encoded DNA. These editing events are dynamically regulated, but few trans regulators of ADARs known in vivo. Here, we screen RNA-binding proteins for roles regulation with knockdown experiments the Drosophila brain. We identify zinc-finger protein at 72D (Zn72D) as a regulator levels majority sites Zn72D both regulates ADAR and interacts an RNA-dependent fashion, similar...
Advances in mRNA technology have enabled mRNA-based therapies to enter a new era of medicine. Such benefit from single, standardized vitro transcription (IVT) manufacturing process applicable wide range targets. This includes several downstream purification steps, which aim eliminate impurities that potentially affect safety and efficacy. However, it is not fully understood are the most critical; hence, some efforts still needed establish correlation between RNA their role limiting...
Toll-like receptors 7 (TLR7) and 8 (TLR8) each sense single-stranded RNA (ssRNA), but their activation results in different immune profiles. Attempts to selectively target either TLR7 or TLR8 have been hindered by high degree of homology. However, recent studies revealed that bind ligands resulting from the processing ssRNA endolysosomal RNases. We demonstrate introducing precise 2′ sugar-modified bases into oligoribonucleotides (ORNs) containing known binding motifs, we could prevent...
Abstract Antigen presentation on MHC class I (MHC-I) is key to the adaptive immune response cancerous cells. Computational prediction of peptide by MHC-I has enabled individualized cancer immunotherapies. Here, we introduce HLApollo, a transformer-based approach with end-to-end modeling sequence, deconvolution, and flanking sequences. To achieve this, develop novel training strategy, negative set switching, which greatly reduces overfitting falsely presumed negatives that are necessarily...
Based on the success of cancer immunotherapy, personalized vaccines have emerged as a leading oncology treatment. Antigen presentation MHC class I (MHC-I) is crucial for adaptive immune response to cells, necessitating highly predictive computational methods model this phenomenon. Here, we introduce HLApollo, transformer-based peptide-MHC-I (pMHC-I) prediction, leveraging language peptides, MHC, and source proteins. HLApollo provides end-to-end treatment MHC-I sequences deconvolution...
Abstract Adenosine-to-Inosine RNA editing is catalyzed by ADAR enzymes that deaminate adenosine to inosine. While many sites are known, few trans regulators have been identified. We perform BioID followed mass-spectrometry identify of ADAR1 and ADAR2 in HeLa M17 neuroblastoma cells. known novel ADAR-interacting proteins. Using ENCODE data we validate characterize a subset the interactors as global or site-specific regulators. Our set includes all four members DZF-domain-containing family...
ABSTRACT Macrophages adopt dynamic cell states with distinct effector functions to maintain tissue homeostasis and respond environmental challenges. During chronic inflammation, macrophage polarization is subverted towards sustained inflammatory which contribute disease, but there limited understanding of the regulatory mechanisms underlying these disease-associated states. Here, we describe a systematic functional genomics approach that combines genome-wide phenotypic screening in primary...
Abstract CD4 T cells have long been known to be critical for priming CD8 cells, a process referred as cell help. Recent data suggested that help may delivered at the surface of conventional type 1 dendritic (cDC1s), which can efficiently present antigens (Ag) on both MHC class I and II molecules. However, actual mechanisms underlying remain poorly characterized. We sought understand how anti-tumor responses are generated in context mRNA vaccines, shown elicit protective and/or cells. For...
<h3>Background</h3> Individualized neoantigen vaccines are showing promise in the adjuvant setting for treatment of patients with cancer.<sup>1 2</sup> In contrast however, clinical activity these has been limited advanced cancers. Thus, characterizing vaccine induced immune responses, and particular, phenotype, longevity, fate vaccine-induced T cells upon entry into tumor tissues is critical to identify therapeutic combination approaches improve benefit. <h3>Methods</h3> Here, utilizing a...
Abstract Adenosine-to-inosine RNA editing, catalyzed by ADAR enzymes, alters sequences from those encoded DNA. These editing events are dynamically regulated, but few trans regulators of ADARs known in vivo . Here, we screen binding proteins for roles regulation using knockdown experiments the Drosophila brain. We identify Zinc-Finger Protein at 72D (Zn72D) as a regulator levels majority sites Zn72D both regulates protein and interacts with an RNA-dependent fashion, similar to ADAR, is...
Abstract Excessive systemic inflammation is characteristic to various acute conditions including sepsis, viral infections and immunotherapy-induced adverse events such as cytokine release syndrome (CRS). Recently, several clinical trials evaluating variants of lipid-formulated RNA vaccines for either cancer or COVID-19 have reported inflammatory responses that limit vaccine dosing in humans. Preclinical studies inbred laboratory mice failed predict these events, suggesting the existence...
<h3>Background</h3> Toll-like receptors (TLRs) are an integral part of innate immune cell activation and play essential role in mounting effective antigen-specific adaptive responses. TLR7 TLR8 highly homologous TLR family members that recognize ssRNA derived from viruses induce distinct cytokine profiles due to differential expression cells. Recent studies demonstrate degraded products generated by endosomal RNases. We hypothesized site-specific modifications foundational sequences...