Biology subjects

Peng, X.

Publications and source records attributed to Peng, X..

At least 91 records · Page 5Linked to original sources

bioRxiv2023

Is M1-L121E a good mimic on microbial rhodopsin? A viewpoint from excited-state dynamics

Microbial rhodopsin, an important photoreceptor protein, has been widely used in several fields, such as optogenetics, biotechnology, and biodevices etc. However, current microbial rhodopsins are all transmembrane proteins, which both complicates the investigation on the photoreaction mechanism and limits their further applications. Therefore, a suitable mimic for microbial rhodopsin can not only provide a better model for understanding the mechanism, but also can extend the applications. The human protein CRABPII turns out to be a good template for design mimics on rhodopsin, due to the convenience in synthesis and the stability after mutations. Recently, Geiger et al. designed a new CRABPII-based mimic M1-L121E on microbial rhodopsin with the correct 13-cis (13C) isomerization after irritation. However, it still remains a question how similar it is compared with the natural microbial rhodopsin, in particular in the aspect of the photoreaction dynamics. In this article, we investigated the excited-state dynamics of this mimic by measuring its transient absorption spectra. Our results reveal that there are two components in the solution of mimic M1-L121E at PH=8, known as protonated Schiff base (PSB) and unprotonated Schiff base (USB) states. In both states, the photoreaction process from 13-cis (13C) to all-trans (AT) is faster than that from the inverse direction. In addition, the photoreaction process in PSB state is faster than that in the USB state. In the end, we compared the isomerization time of the PSB state with the properties of the microbial rhodopsin, and confirmed that the mimic M1-L121E indeed captures the main feature of the rhodopsin and is a good model of microbial rhodopsin in the photoreaction dynamics. However, our results also reveal significant differences in the excited-state dynamics of the mimic relative to the natural microbial rhodopsin, including the slower PSB isomerization rates in both 13C-AT and AT-13C directions, as well as the unusual USB photoreaction dynamics at PH=8. Such unique properties have not been observed in the natural rhodopsin, which could further deepen the understanding in photoreaction mechanism of the photosensitive proteins.

biophysics↗

bioRxiv2023

Identification of potential distribution area for the sweet cherry (Prunus avium) by the MaxEnt model

The potential distribution of species offers important information for species management, especially for fruit trees with economic value. The sweet cherry is a tree species with higher economic value among deciduous fruit trees in north China. Herein, its potential distributions were modeled under current conditions. The performances of this model were excellent with AUCs of >0.9 for model training and testing. The key factors identified were the thermal factors (min temperature of coldest month (bio06) from -14.5 to 4.5{degrees}C, the mean temperature of warmest quarter (bio10) from 21.0 to 28.0{degrees}C), followed by water factor (the annual precipitation (bio12) from 500 to 1200 mm). Its suitable region in China mainly is located on 6 geographical regions including southwest China (eastern Sichuan, northeast and main urban areas of Chongqing, mid-western Guizhou and mid-northern Yunnan), northwest China (mid-southern Shaanxi, southern Ningxia mid-southern and eastern Gansu), northeast China (Coastal region of Liaoning), central China (most of Henan, mid-northern Hubei and central Hunan), north China (Beijing, Tianjing, mid-southern Shanxi), east China (Shanghai, Jiangsu, Shandong, central Zhejiang, central and northern Anhui and eastern Jiangxi) and south China (western Guangxi). Relative to their actual distributions, Hubei, Hunan and Anhui etc have been identified to have some potentially suitable areas for these sweet cherries. Among them, these 9 provinces or cities (Shaanxi, Beijing, Tianjing, Shanxi, Hebei, Henan, Shanghai, Jiangsu and Shandong) are main regions for its current development and utilization, followed by Sichuan, Guizhou,Yunnan, Gansu, Liaoning, Hubei, Zhejiang and Guangxi etc. The results can be adopted to identify the suitable areas for its introduction and cultivation to avoid the losses of human labor, material and financial resources due to improper decision, and to provide a scientific basis for its current introduction, cultivation and management.

ecology↗

bioRxiv2023

Integrating large-scale meta-GWAS and PigGTEx resources to decipher the genetic basis of complex traits in pig.

Understanding the molecular and cellular mechanisms that underlie complex traits in pigs is crucial for enhancing their genetic improvement program and unleashing their substantial potentials in human biomedicine research. Here, we conducted a meta-GWAS analysis for 232 complex traits with 28.3 million imputed whole-genome sequence variants in 70,328 individuals from 14 pig breeds. We identified a total of 6,878 genomic regions associated with 139 complex traits. By integrating with the Pig Genotype-Tissue Expression (PigGTEx) resource, we systemically explored the biological context and regulatory circuits through which these trait-associated variants act and finally prioritized 16,664 variant-gene-tissue-trait circuits. For instance, rs344053754 regulates the expression of UGT2B31 in the liver by affecting the activity of regulatory elements and ultimately influences litter weight at weaning. Furthermore, we investigated the conservation of genetic and regulatory mechanisms underlying 136 human traits and 232 pig traits. Overall, our multi-breed meta-GWAS in pigs provides invaluable resources and novel insights for understanding the regulatory and evolutionary mechanisms of complex traits in both pigs and humans.

genetics↗

bioRxiv2023

Discovery of peptides for targeted delivery of mRNA lipid nanoparticles to cystic fibrosis lung epithelia

For cystic fibrosis (CF) patients, a lung targeted gene therapy would significantly alleviate pulmonary complications associated with morbidity and mortality. However, mucus in the airways and cell entry pose huge delivery barriers for local gene therapy. Here, we used phage display technology to select for and identify mucus- and cell-penetrating peptides against primary human bronchial epithelial cells (pHBECs) from CF patients cultured at air-liquid interface (ALI). At ALI, pHBECs produce mucus and reflect CF disease pathology, making it a clinically relevant model. Using this model, we discovered a lead candidate peptide, and incorporated it into lipid nanoparticles (LNPs) to deliver mRNA to pHBECs and mouse lungs in vivo. Compared to LNPs without our peptide, peptide-LNPs demonstrated 7.8-fold and 4.8-fold higher mRNA expression in vitro and in vivo, respectively. Since gene delivery to pHBECs is a significant challenge, we are encouraged by these results and anticipate that our peptide could be used to successfully deliver CF gene therapies in future work.

bioengineering↗

bioRxiv2023

The Diversity of NLRs in Brassica rapa Pan-genome

The species Brassica rapa is mainly cultivated as a vegetable crop with high economic value. But infectious diseases, such as soft rot disease and clubroot disease can cause severe yield losses. Introducing resistance genes through breeding is an efficient and sustainable way to reduce the susceptibility and improve the yield of crops. Nucleotide-Binding Leucine-Rich Repeat (NLR) genes are the main types of resistance genes. They can recognize pathogen effectors and initiate downstream immune response. However, the intraspecific diversity of NLR genes in Brassica rapa has remained unknown. Based on domain similarity search and machine learning pipeline, we identified 2188 NLRs in 17 accessions of Brassica rapa genomes, which constitute the species-wide pan-NLRome in Brassica rapa. The diversity of the four types of NLR genes are significantly different in the aspects of chromosome location, number stability, integrated domains (IDs), evolutionary trajectory, and positive selection sites. Phylogenetic analyses show TNL-type NLRs whose N terminus contain Toll/interleukin-1 receptor (TIR) domain experienced accession-specific expansion. Moreover, the expanded TNL-type NLRs carry more positively selected amino acid residues which are mainly located on the protein surface based on their 3D structures. These evidences might imply their important biological function in perceiving pathogen effectors. Taken together, our study provides better insights into the diversity and variation of NLR genes in Brassica rapa pangemone, which can facilitate the biofunction assigning, cloning, and subsequent application in breeding programs.

genomics↗

bioRxiv2023

Recombinant Ranpirnase enhances the expression of co-transfected mRNA by modulating cellular metabolic activity

As the worlds first approved prophylactic mRNA vaccine, the development of the Covid-19 mRNA vaccine marks a milestone in mRNA therapeutics. However, achieving efficient transgene expression in therapeutic applications such as protein replacement and cancer therapeutical vaccines remains challenging. This study explores the use of recombinant Ranpirnase, a small ribonuclease, as a novel expression-enhancing tool for mRNA-based therapeutics. In Balb/c mice, co-expression of Ranpirnase significantly increased transgene expression levels by 3-to 6-fold and prolonged expression duration by more than 85%, regardless of mRNA nucleoside modification status. Recombinant Ranpirnase induces a cytostatic state in host cells, stabilizing mRNA and protein transcripts, thereby enhancing transgene expression. Importantly, co-expression of Ranpirnase recombinants did not cause detectable cytotoxicity or alter the tissue distribution of transgene expression, ensuring safety and tolerability at higher translation levels. The compact size of the recombinant Ranpirnase gene allows for seamless fusion with the target gene or co-transfection with existing delivery technologies. Altogether, recombinant Ranpirnase shows promise as an expression-enhancing element in mRNA-based therapeutics, including veterinary applications.

molecular biology↗

bioRxiv2023

Temporal transcriptomic dynamics in developing macaque neocortex

Despite intense research on mice, the transcriptional regulation of neocortical neurogenesis remains limited in humans and non-human primates. Cortical development in rhesus macaque is known to recapitulate multiple facets of cortical development in humans, including the complex composition of neural stem cells and the thicker supragranular layer. To characterize temporal shifts in transcriptomic programming responsible for differentiation from stem cells to neurons, we sampled parietal lobes of rhesus macaque at E40, E50, E70, E80, and E90, spanning the full period of prenatal neurogenesis. Single-cell RNA sequencing produced a transcriptomic atlas of the developing rhesus macaque neocortex parietal lobe. Identification of distinct cell types and neural stem cells emerging in different developmental stages revealed a terminally bifurcating trajectory from stem cells to neurons. Notably, deep-layer neurons appear in the early stages of neurogenesis, while upper-layer neurons appear later. While these different lineages show overlap in their differentiation program, cell fates are determined post-mitotically. Pseudotime trajectories from vRGs to oRGs revealed differences in dynamic gene expression profiles and identified divergence in their activation of BMP, FGF, and WNT signaling pathways. These results provide a comprehensive picture of the temporal patterns of gene expression leading to different fates of radial glial progenitors during neocortex layer formation.

developmental biology↗

bioRxiv2023

Beyond venomous fangs: Uloboridae spiders have lost their venom apparatus but not their toxins

Venom, one of natures most potent secretions, has played a crucial role in the evolutionary success of many animal groups, including spiders. However, Uloboridae spiders appear to lack venom and capture their prey, unlike venomous spiders, by extensive silk-wrapping and regurgitation of digestive fluids onto the entire prey. A prevailing hypothesis posits that toxins may have been reallocated from the venom to alternative secretions, like silk or digestive fluids. Yet, whether uloborids have retained venom toxins and the mechanisms underlying prey immobilisation remain unresolved. Here, we employed a multi-disciplinary approach to assess the absence of venom glands in Uluborus plumipes, toxin gene expression and toxicity of digestive proteins. Our findings confirm that U. plumipes lacks a venom apparatus, while neurotoxin-like transcripts were highly expressed in the digestive system. Midgut gland extract had comparable toxicity levels to that of the venomous Parasteatoda tepidariorum. However, no inhibitory effects on sodium nor potassium channels were observed, indicating a different toxic mechanism. These findings support the hypothesis that Uloboridae spiders have lost their venom apparatus while retaining toxin-like genes. The potent toxicity of their digestive fluids, a trait conserved across spiders, likely compensate for the absence of venom, ensuring effective prey immobilisation and digestion.

evolutionary biology↗

bioRxiv2023

Effect of Acute Stress on Working Memory in Pilots: Investigating the Modulatory Role of Memory Load

The effect of acute stress on working memory (WM) has not been extensively investigated in demanding tasks, although many practitioners, such as pilots, frequently face varying working memory demands. The current study investigated how acute stress modulates pilots WM performance. Forty-two pilots were randomly assigned to the stress group or the control group. The stress group experienced acute stress induced by the modified Trier Social Stress Test (TSST), whereas the control group did not receive any stress induction. Both groups performed N-back tasks under varying degrees of memory load (0-back, 1-back, and 2-back). State-Trait Anxiety Inventory scores, heart rates, and salivary cortisol concentrations were measured in the experiment to determine the extent of induced stress. The results revealed that (1) The modified TSST effectively induced acute stress in the stress group. (2) As rising of memory load, the reaction time expectedly increased while accuracy decreased. (3) An interaction between the stress and control group was found for accuracy, indicating that acute stress might contribute to higher accuracy in moderate WM load (1-back). These suggestions support the emotion regulation hypothesis, in which acute stress induces heightened emotional states that impact WM performance. Furthermore, the current study explored the interplay between acute stress and memory load in a specific population, offering insights into potential pilots stress management strategies and training programs to improve pilots WM abilities. These applications would be beneficial for strengthening pilots coping mechanisms in emergencies and guaranteeing flight safety.

physiology↗

bioRxiv2023

De novo design of a β-helix tau protein scaffold: An oligomer-selective vaccine immunogen candidate for Alzheimer's disease

Tau pathology is associated with many neurodegenetive disorders, including Alzheimers disease (AD), where the spatio-temporal pattern of tau neurofibrillary tangles strongly correlates with disease progression, which motivates therapeutics selective for misfolded tau. Here, we introduce a new avidity-enhanced, multi-epitope approach for protein misfolding immunogen design, which is predicted to mimic the conformational state of an exposed epitope in toxic tau oligomers. A predicted oligomer-selective tau epitope 343KLDFK347 was scaffolded by designing a {beta}-helix structure that incorporated multiple instances of the 16-residue tau fragment 339VKSEKLDFKDRVQSKI354. Largescale conformational ensemble analyses involving Jensen-Shannon Divergence and the embedding depth [D] showed that the multi-epitope scaffolding approach, employed in designing the {beta}-helix scaffold, was predicted to better discriminate toxic tau oligomers than other "monovalent" strategies utilizing a single instance of an epitope for vaccine immunogen design. Using Rosetta, 10,000 sequences were designed and screened for the linker portions of the {beta}-helix scaffold, along with a C-terminal stabilizing -helix that interacts with the linkers, to optimize the folded structure and stability of the scaffold. Structures were ranked by energy, and the lowest 1% (82 unique sequences) were verified using AlphaFold. Several selection criteria involving AlphaFold are implemented to obtain a lead designed sequence. The structure was further predicted to have free energetic stability by using Hamiltonian replica exchange molecular dynamics (MD) simulations. The synthesized {beta}-helix scaffold showed direct binding in surface plasmon resonance (SPR) experiments to several antibodies that were raised to the structured epitope using a designed cyclic peptide. Moreover the strength of binding of these antibodies to in vitro tau oligomers correlated with the strength of binding to the {beta}-helix construct, suggesting that the construct presents an oligomer-like conformation and may thus constitute an effective oligomer-selective immunogen.

bioengineering↗

bioRxiv2023

Pontiella agarivorans sp. nov., a novel marine anaerobic bacterium capable of degrading macroalgal polysaccharides and fixing nitrogen

Marine macroalgae produce abundant and diverse polysaccharides which contribute substantially to the organic matter exported to the deep ocean. Microbial degradation of these polysaccharides plays an important role in the turnover of macroalgal biomass. Various members of the Planctomycetes-Verrucomicrobia-Chlamydia (PVC) superphylum are degraders of recalcitrant polysaccharides in widespread anoxic environments. In this study, we isolated a novel anaerobic bacterial strain NLcol2T from microbial mats on the surface of marine sediments offshore Santa Barbara, California, USA. Based on 16S rRNA gene and phylogenomic analyses, strain NLcol2T represents a novel species within the Pontiella genus in the Kiritimaitellaeota phylum (within the PVC superphylum). Strain NLcol2T is able to utilize various monosaccharides, disaccharides, and macroalgal polysaccharides such as agar and iota-carrageenan. A near-complete genome also revealed an extensive metabolic capacity for anaerobic degradation of sulfated polysaccharides, as evidenced by 202 carbohydrate-active enzymes (CAZymes) and 165 sulfatases. Additionally, its ability of nitrogen fixation was confirmed by nitrogenase activity detected during growth on nitrogen-free medium, and the presence of nitrogenases (nifDKH) encoded in the genome. Based on the physiological and genomic analyses, this strain represents a group of bacteria that may play an important role in the degradation of macroalgal polysaccharides and with relevance to the biogeochemical cycling of carbon, sulfur, and nitrogen in marine environments. Strain NLcol2T (= DSM 113125T = MCCC 1K08672) is proposed to be the type strain of a novel species in Pontiella genus, and the name Pontiella agarivorans sp. nov. is proposed.

microbiology↗

bioRxiv2023

YAP/TAZ enhance P-body formation to promote tumorigenesis

The role of Processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P- body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P- body formation in CRC cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration and tumor growth induced by overexpression of YAP5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed codependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1 and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.

cell biology↗

bioRxiv2023

Piezo1-dependent regulation of pericyte proliferation by blood flow during brain vascular development

Blood flow is known to regulate cerebrovascular development through acting on vascular endothelial cells (ECs). As an indispensable component of the cerebrovascular unit, brain pericytes physically couple with ECs with the highest density in the body and play vital roles in blood-brain barrier integrity maintenance and neurovascular coupling. However, it remains unclear whether blood flow affects the development of brain pericytes. Here, we report that blood flow can promote brain pericyte proliferation, which depends on the mechanosensitive ion channel Piezo1. Using in vivo time-lapse imaging of larval zebrafish, we monitored the developmental dynamics of brain pericytes and found that they proliferated to expand their population and increase their coverage on brain vessels. In combination with pharmacological and genetic approaches, we demonstrate that the proliferation of brain pericytes can be enhanced by increased blood flow through Piezo1 expressed in ECs. Furthermore, EC-intrinsic Notch signaling was found to be downstream of Piezo1 for the blood flow regulation of brain pericyte proliferation. Thus, our findings reveal an important role of blood flow for pericyte proliferation, extending the functional spectrum of hemodynamics on the development of cerebral vasculature.

developmental biology↗

bioRxiv2023

Uncovering the hidden structure of dynamic T cell composition in peripheral blood during cancer immunotherapy: a topic modeling approach

Immune checkpoint inhibitors (ICIs), now mainstays in the treatment of cancer treatment, show great potential but only benefit a subset of patients. A more complete understanding of the immunological mechanisms and pharmacodynamics of ICI in cancer patients will help identify the patients most likely to benefit and will generate knowledge for the development of next-generation ICI regimens. We set out to interrogate the early temporal evolution of T cell populations from longitudinal single-cell flow cytometry data. We developed an innovative statistical and computational approach using a Latent Dirichlet Allocation (LDA) model that extends the concept of topic modeling used in text mining. This powerful unsupervised learning tool allows us to discover compositional topics within immune cell populations that have distinct functional and differentiation states and are biologically and clinically relevant. To illustrate the models utility, we analyzed [~]17 million T cells obtained from 138 pre- and on-treatment peripheral blood samples from a cohort of melanoma patients treated with ICIs. We identified three latent dynamic topics: a T-cell exhaustion topic that recapitulates a LAG3+ predominant patient subgroup with poor clinical outcome; a naive topic that shows association with immune-related toxicity; and an immune activation topic that emerges upon ICI treatment. We identified that a patient subgroup with a high baseline of the naive topic has a higher toxicity grade. While the current application is demonstrated using flow cytometry data, our approach has broader utility and creates a new direction for translating single-cell data into biological and clinical insights.

bioinformatics↗

bioRxiv2023

PEELing: an integrated and user-centric platform for cell-surface proteomics analysis

SummaryMolecular compartmentalization is vital for cellular physiology. Spatially-resolved proteomics allows biologists to survey protein composition and dynamics with subcellular resolution. Here we present PEELing, an integrated package and user-friendly web service for analyzing spatially- resolved proteomics data. PEELing assesses data quality using curated or user-defined references, performs cutoff analysis to remove contaminants, connects to databases for functional annotation, and generates data visualizations--providing a streamlined and reproducible workflow to explore spatially-resolved proteomics data. Availability and ImplementationPEELing and its tutorial are publicly available at https://peeling.janelia.org/. A Python package of PEELing is available at https://github.com/JaneliaSciComp/peeling/. ContactTechnical support for PEELing: peeling@janelia.hhmi.org.

systems biology↗

bioRxiv2023

Four additional natural 7-deazaguanine derivatives in phages and how to make them

Bacteriophages and bacteria are engaged in a constant arms race, continually evolving new molecular tools to survive one another. To protect their genomic DNA from restriction enzymes, the most common bacterial defence systems, double-stranded DNA phages have evolved complex modifications that affect all four bases. This study focuses on modifications at position 7 of guanines. Eight derivatives of 7-deazaguanines were identified, including four previously unknown ones: 2-deoxy-7-(methylamino)methyl-7-deazaguanine (mdPreQ1), 2-deoxy-7-(formylamino)methyl-7-deazaguanine (fdPreQ1), 2-deoxy-7-deazaguanine (dDG), and 2-deoxy-7-carboxy-7-deazaguanine (dCDG). These modifications are inserted in DNA by a guanine transglycosylase named DpdA. Three subfamilies of DpdA had been previously characterized: bDpdA, DpdA1, and DpdA2. Two additional subfamilies were identified in this work: DpdA3, which allows for complete replacement of the guanines, and DpdA4, which is specific to archaeal viruses. Transglycosylases have now been identified in all phages and viruses carrying 7-deazaguanine modifications, indicating that the insertion of these modifications is a post-replication event. Three enzymes were predicted to be involved in the biosynthesis of these newly identified DNA modifications: 7-carboxy-7-deazaguanine decarboxylase (DpdL), dPreQ1 formyltransferase (DpdN), and dPreQ1 methyltransferase (DpdM), which was experimentally validated and harbors a unique fold not previously observed for nucleic acid methylases.

genomics↗

bioRxiv2023

The central nervous system is a potential reservoir and possible origin of drug resistance in HBV

The significance of HBV in cerebrospinal fluid (CSF) is unclear. In the present study, synchronous serum and CSF samples were collected from 13 patients. HBV-DNA, full-length genome, quasispecies, phylogenetic tree, compartmentalization and mutation of reverse transcriptase (RT) region analyses were performed based on PCR and sequencing methods. We found HBV-DNA was detected in the CSF of 3 antiviral-naive patients and one patient after successful antiviral therapy. Complete full-length HBV genomes were isolated from the CSF of 5 patients, including 2 patients with undetectable serum HBV-DNA. Ten patients exhibited distinct CSF-serum quasispecies, 8 harbored independent CSF-serum genetic compartmentalization and phylogenetic trees, and 5 patients presented lamivudine/entecavir-associated resistance mutations in only the CSF. The frequencies of rtL180M and rtM204I/V mutations in both serum and CSF were higher in HIV/HBV-coinfected patients than in HBV-monoinfected patients (serum: rtL180M: 3.9% vs. 0, P = 0.004; rtM204I/V: 21.3% vs. 0, P < 0.001; CSF: rtL180M: 7.6% vs. 0, P = 0.026; rtM204I/V 7.6% vs. 1.6%, P = 0.097). Our data suggested CSF is a potential HBV reservoir, and HBV in CSF harbors distinct evolution and mutation models from that in serum. HIV infection increases the possibility of HBV rtL180M and rtM204I/V mutations in both serum and CSF.

evolutionary biology↗

bioRxiv2023

Improving mRNA vaccine safety and efficiency with cationized lipid nanoparticle formula

The widespread use of Covid-19 mRNA vaccines has highlighted the need to address rare but concerning side effects. Systemic off-target gene expression has been identified as a primary cause of acute adverse reactions and side effects associated with nucleoside-modified mRNA vaccines. In this study, we incorporated the permanent cationic lipid Dotap component into the mRNA-LNP formula associated with the FDA-approved mRNA vaccine Comirnaty to create a novel positively charged LNP carrier for mRNA vaccine delivery. Using the optimized LNP formula to prepare SARS-Cov-2 Spike mRNA vaccines for immunogenicity testing, Balb/c mice exhibited improved immunogenicity kinetics with initial antibody titers being lower but showing a continuous upward trend, ultimately reaching levels comparable to those of control mRNA vaccines 8 weeks after boost immunization. The mRNA vaccines encapsulated in the modified LNPs have demonstrated a superior safety profile in respect to systemic delivery of LNP constituents, off-target gene expression, and the systemic pro-inflammatory stimulation. Consequently, it may represent a safer alternative of conventional mRNA-LNP vaccines.

synthetic biology↗