中文摘要：
将信使核糖核酸（mRNA）经全身递送至肝脏、脾脏、肺部以外的脏器，目前仍存在较大技术难题。为攻克该瓶颈，本研究提出假设：调整纳米颗粒化学组分与给药途径，或可实现网状内皮系统以外脏器的 mRNA 靶向蛋白表达。本文报道一种利用脂质纳米颗粒高效、特异性靶向胰腺递送 mRNA 的技术方案。实验结果证实，腹腔注射搭载阳离子辅助脂质的脂质纳米颗粒，能够在胰腺组织中实现强效且特异的目标蛋白表达，且蛋白主要在分泌胰岛素的 β 细胞内生成。研究进一步证实，胰腺组织的 mRNA 递送效应依赖腹腔巨噬细胞分泌外泌体介导的水平基因转移；该调控 mRNA 脂质纳米颗粒递送效率的机制此前尚未得到充分关注。本递送策略有望为糖尿病、胰腺癌等难治性胰腺疾病的基因治疗提供全新技术支撑。
英文摘要：
Systemic messenger RNA (mRNA) delivery to organs outside the liver, spleen, and lungs remains challenging. To overcome this issue, we hypothesized that altering nanoparticle chemistry and administration routes may enable mRNA-induced protein expression outside of the reticuloendothelial system. Here, we describe a strategy for delivering mRNA potently and specifically to the pancreas using lipid nanoparticles. Our results show that delivering lipid nanoparticles containing cationic helper lipids by intraperitoneal administration produces robust and specific protein expression in the pancreas. Most resultant protein expression occurred within insulin-producing β cells. Last, we found that pancreatic mRNA delivery was dependent on horizontal gene transfer by peritoneal macrophage exosome secretion, an underappreciated mechanism that influences the delivery of mRNA lipid nanoparticles. We anticipate that this strategy will enable gene therapies for intractable pancreatic diseases such as diabetes and cancer.
论文信息：
论文题目：Ionizable lipid nanoparticles deliver mRNA to pancreatic β cells via macrophage-mediated gene transfer
期刊名称：Science Advances
时间期卷：Vol 9, Issue4(2023)
在线时间：2023年1月27日
DOI: 10.1126/sciadv.ade1444
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes&Control Liposomes
办事处：靶点科技
Clodronate Liposomes氯膦酸盐脂质体腹腔注射清除巨噬细胞后，特异性靶向胰腺递送 mRNA脂质纳米颗粒递送。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances：可电离脂质纳米颗粒通过巨噬细胞介导的基因递送途径，将信使核糖核酸递送至胰腺 β 细胞。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法：
All animal experiments were conducted using institutionally approved protocols (Institutional Animal Care and Use Committee). C57BL/6 mice (female unless otherwise indicated) were obtained from Charles River Laboratories, Wilmington, MA. STZ mice (males) and NOD and NOD/SCID mice (females) were obtained from the Jackson Laboratory (Bar Harbor, ME). STZ mice exhibited hyperglycemia (blood glucose > 250 mg/dl) upon arrival. In experiments involving clodronate liposomes, clodronate liposomes and control liposomes were purchased from Liposoma (Amsterdam, The Netherlands). Mice received intraperitoneal injections of 200 μl of clodronate or control liposomes 48 hours before LNP treatment. For fluorescence and luminescence studies, dissected organs were imaged using an IVIS (Perkin Elmer). In experiments using mRNA encoding luciferase, mice received an intraperitoneal injection of 130 μl of d-luciferin (30 mg/ml) 15 min before imaging. Blood samples were drawn via submandibular bleed and collected in Microtainer Serum Separator tubes (Becton Dickinson, Franklin Lakes, NJ).
巨噬细胞清除材料和方法文献截图：
