Distinct Inflammatory Programs Underlie the Intramuscular Lipid Nanoparticle Response

炎症反应 纳米颗粒 炎症 纳米技术 材料科学 化学 医学 免疫学
作者
William Dowell,Jacob Dearborn,Sylvester Languon,Zachary D. Miller,Tylar Kirch,Stephen Paige,Olivia Garvin,Lily Kjendal,Ethan Harby,Adam B. Zuchowski,Emily R. Clark,Carlos Lescieur-Garcia,Jesse Vix,Amy Schumer,Somen K Mistri,Deena B. Snoke,Amber L. Doiron,Kalev Freeman,Michael J. Toth,Matthew E. Poynter
出处
期刊:ACS Nano [American Chemical Society]
被引量:1
标识
DOI:10.1021/acsnano.4c08490
摘要

Developments in mRNA/lipid nanoparticle (LNP) technology have advanced the fields of vaccinology and gene therapy, raising questions about immunogenicity. While some mRNA/LNPs generate an adjuvant-like environment in muscle tissue, other mRNA/LNPs are distinct in their capacity for multiple rounds of therapeutic delivery. We evaluate the adjuvancy of components of mRNA/LNPs by phenotyping cellular infiltrate at injection sites, tracking uptake by immune cells, and assessing the inflammatory state. Delivery of 9 common, but chemically distinct, LNPs to muscle revealed two classes of inflammatory gene expression programs: inflammatory (Class A) and noninflammatory (Class B). We find that intramuscular injection with Class A, but not Class B, empty LNPs (eLNPs) induce robust neutrophil infiltration into muscle within 2 h and a diverse myeloid population within 24 h. Single-cell RNA sequencing revealed SM-102-mediated expression of inflammatory chemokines by myeloid infiltrates within muscle 1 day after injection. Surprisingly, we found direct transfection of muscle infiltrating myeloid cells and splenocytes 24 h after intramuscular mRNA/LNP administration. Transfected myeloid cells within the muscle exhibit an activated phenotype 24 h after injection. Similarly, directly transfected splenic lymphocytes and dendritic cells (DCs) are differentially activated by Class A or Class B containing mRNA/LNP. Within the splenic DC compartment, type II conventional DCs (cDC2s) are directly transfected and activated by Class A mRNA/LNP. Together, we show that mRNA and LNPs work synergistically to provide the necessary innate immune stimuli required for effective vaccination. Importantly, this work provides a design framework for vaccines and therapeutics alike.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
Inory007完成签到,获得积分10
刚刚
刚刚
ajie发布了新的文献求助30
刚刚
kk发布了新的文献求助10
1秒前
孔大漂亮完成签到,获得积分10
1秒前
慕青应助虚心的雁采纳,获得10
2秒前
Jjj发布了新的文献求助10
2秒前
LML完成签到,获得积分10
2秒前
FashionBoy应助joyce采纳,获得30
2秒前
吉宝发布了新的文献求助10
3秒前
Lky发布了新的文献求助10
3秒前
4秒前
群木成林完成签到,获得积分10
4秒前
量子星尘发布了新的文献求助10
4秒前
kingwill完成签到,获得积分0
4秒前
5秒前
6秒前
呓语完成签到,获得积分10
6秒前
Dsivan应助旦皋采纳,获得20
6秒前
7秒前
FancyShi发布了新的文献求助10
7秒前
8秒前
SYLH应助优秀的映萱采纳,获得10
8秒前
9秒前
李健应助7w采纳,获得10
9秒前
9秒前
邓佳鑫Alan应助单纯血茗采纳,获得10
10秒前
邓佳鑫Alan应助单纯血茗采纳,获得10
10秒前
张博发布了新的文献求助10
10秒前
wanci应助SS是采纳,获得10
10秒前
11秒前
iNk应助木又采纳,获得20
12秒前
我要早日毕业完成签到,获得积分10
12秒前
Jindyla发布了新的文献求助10
12秒前
Hascy发布了新的文献求助10
12秒前
xiaodaiaa发布了新的文献求助10
12秒前
SolderOH完成签到,获得积分10
12秒前
13秒前
14秒前
jaytotti完成签到,获得积分10
14秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
A new approach to the extrapolation of accelerated life test data 1000
徐淮辽南地区新元古代叠层石及生物地层 500
Coking simulation aids on-stream time 450
康复物理因子治疗 400
北师大毕业论文 基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 390
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4016278
求助须知:如何正确求助?哪些是违规求助? 3556388
关于积分的说明 11320934
捐赠科研通 3289218
什么是DOI,文献DOI怎么找? 1812421
邀请新用户注册赠送积分活动 887940
科研通“疑难数据库(出版商)”最低求助积分说明 812060