更新于：2024-11-01

Multiple Sulfatase Deficiency Disease

多发性硫酸脂酶缺乏症

更新于：2024-11-01

基本信息

别名

Austin syndrome、Juvenile Sulfatidoses、Juvenile Sulfatidosis

+ [36]

简介

An inherited metabolic disorder characterized by the intralysosomal accumulation of sulfur-containing lipids (sulfatides) and MUCOPOLYSACCHARIDES. Excess levels of both substrates are present in urine. This is a disorder of multiple sulfatase (arylsulfatases A, B, and C) deficiency which is caused by the mutation of sulfatase-modifying factor-1. Neurological deterioration is rapid.

关联

项与多发性硫酸脂酶缺乏症相关的药物

AAV9-hSUMF1 (NCATS/NIH)

靶点

SUMF1

作用机制

SUMF1调节剂

在研机构

National Center for Advancing Translational Sciences [+1]

原研机构

National Center for Advancing Translational Sciences [+1]

在研适应症

多发性硫酸脂酶缺乏症

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与多发性硫酸脂酶缺乏症相关的临床试验

NCT05606549 / RecruitingN/AIIT

Effect of Marital Self Disclosure Intervention on Fear of Cancer Recurrence and Dyadic Coping Ability Among Gastric Cancer Survivors and Their Spouse

The goal of this clinical trial is to explores the effect of marital self disclosure intervention on fear of cancer recurrence and dyadic coping ability in gastric cancer survivors and their spouses. The main questions are: What is the level of fear of cancer recurrence among gastric cancer survivors and their spouse? What is the level of dyadic coping ability among gastric cancer survivors and their spouse?What is the effect of marital self-disclosure intervention on fear of cancer recurrence and dyadic coping ability in the gastric cancer survivors and their spouses? Participants will accept the intervention of marital self disclosure for 4 times (4 cycles of chemotherapy) with different topics. Researchers will compare with control group to see if the level of fear of cancer recurrence and dyadic coping ability will be improved.

开始日期2022-10-19

申办/合作机构

University of Malaya

[+2]

IRCT20210413050958N5 / Recruiting临床2期IIT

The effects of N-Acetyl-L-Leucine on the improvement of symptoms in A patient with Multiple Sulfatase Deficiency

开始日期2022-05-31

申办/合作机构

Mashhad University of Medical Sciences

IRCT20130829014521N17 / Completed临床2期IIT

Investigation of the therapeutic effects of Trehalose in a patient witn multiple sulfatase deficiency (MSD)

开始日期2021-02-19

申办/合作机构

Mashhad University of Medical Sciences

100 项与多发性硫酸脂酶缺乏症相关的临床结果

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100 项与多发性硫酸脂酶缺乏症相关的转化医学

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0 项与多发性硫酸脂酶缺乏症相关的专利（医药）

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1,485

项与多发性硫酸脂酶缺乏症相关的文献（医药）

2025-01-01·Applied Ergonomics

Including the ergonomist's voice in integrating MSD prevention and psychological health and safety: Challenges, tools, and considerations

Article

作者: Van Eerd, D. ; O'Reilly, H ; O'Reilly, H. ; Van Eerd, D

The purpose of this study was to gather ergonomists' perspectives and experiences, describing current challenges and contextual considerations in risk assessment, exploring how ergonomists are currently integrating the multiple domains of ergonomics for MSD and/or psychological health and safety and highlighting key considerations in the design and format of future tools. In-depth, semi-structured interviews were conducted with twenty Canadian ergonomists to explore risk assessment tool use, favoured characteristics and format of tools, commonly addressed risk factors in their practice, and tools relating to both MSD prevention and psychological health and safety. The range of practitioner years of experience highlighted differing needs and approaches to the use and formatting of risk assessment tools. Practitioners reported using quantitative outcomes (levels of risk, values) from traditional physical tools complemented by a general observation of psychosocial or organizational factors. Though many respondents had not yet encountered the need for psychological injury assessment in their sectors it was identified as a quickly emerging area citing a need for valid and reliable tools. Practitioners noted a lack of available tools that integrated cognitive and psychosocial items presenting a future challenge for integrated tools that covered multiple ergonomic domains. Along with recommendations for future tool development, the authors reflect on the process of qualitative inquiry as an essential step in the risk assessment process. Future studies will be needed to develop and evaluate measurement properties of integrating psychosocial factors and their respective tools in traditional MSD assessment.

2025-01-01·Journal of Affective Disorders

The association of pain screening and pain level with suicide among US veterans with comorbid musculoskeletal and bipolar disorder diagnoses

Article

作者: Snow, Jennifer L. ; Travaglini, Letitia E. ; Snow, Jennifer L ; Goulet, Joseph L ; Goulet, Joseph L. ; Travaglini, Letitia E ; Abel, Erica A. ; Abel, Erica A

BACKGROUNDHigh suicide rates are documented among persons with bipolar disorder diagnoses and pain diagnoses, but few studies have examined the association of pain with suicide mortality in individuals with comorbid pain and bipolar disorders. This study assessed the association of pain screening and pain severity with suicide mortality among veterans with comorbid bipolar and musculoskeletal disorder (MSD) diagnoses.METHODSA retrospective cohort study was conducted on 168,021 patients within the Veterans Health Administration (VHA) who received an MSD diagnosis from 2000 to 2015 and had a bipolar disorder diagnosis. Pain severity, comorbidities, demographics, and suicide mortality were extracted from VHA databases. Poisson regression examined relative risk of suicide by the presence pain screening and pain severity ratings.RESULTSPain was assessed in 72.73 % of veterans. Suicide risk was greater in those not assessed (0.98 % versus 0.77 % in assessed group). However, this result did not persist after adjusting for covariates (RR = 1.06). Among those assessed, higher suicide risk was associated with moderate (RR = 1.10), severe pain (RR = 1.06), and no pain (reference) relative to mild pain (RR = 0.99). Major depression, substance use disorders, and prescribed opioids and benzodiazepines increased risk.LIMITATIONSData were obtained from medical records; diagnoses were not confirmed via formal assessment, and no information was available on actual medication use or purpose. Over 25 % of the sample were missing pain severity ratings, which could have affected results.CONCLUSIONSSuicide risk factors among persons with bipolar disorder are complex and multifactorial. Providers should prioritize suicide prevention efforts following new onset or worsening pain.

2025-01-01·Journal of Ethnopharmacology

Aphrodisiac activity of aqueous extract of Anthonotha macrophylla (P. Beauv) leaves in paroxetine-induced sexual dysfunction male Wistar rats

Article

作者: OLUTOYE, Abdulquadri Funmbi ; Yakubu, Musa Toyin ; YAKUBU, Musa Toyin ; Olutoye, Abdulquadri Funmbi

ETHNO-PHARMACOLOGICAL RELEVANCEAnthonotha macrophylla, a plant with extensive ethnomedicinal uses, has various parts attributed to healing properties. The bark is claimed to be used to treat venereal diseases while the roots are used to treat intestinal discomfort. Gum extract from the bark provides pain relief, while the leaves are used for treating gonorrhoea, diarrhoea, and malaria. Additionally, the leaves are believed to enhance sexual behaviour. Although the age-long folkloric use of Anthonotha macrophylla leaf as aphrodisiac in female rats was substantiated with scientific evidence, the study did not account for the aphrodisiac activity in paroxetine-induced sexual dysfunction in male rat model.AIM OF THE STUDYThis study investigated the aphrodisiac activity of aqueous extract of Anthonotha macrophylla leaves (AEAML) in paroxetine-induced sexual dysfunction male rats (PISDMR).MATERIALS AND METHODSForty-two male rats (144.86 ± 1.21 g) were assigned into six groups (A-F). Group A received distilled water only, while PISDMR in Groups B, C, D, E and F received distilled water, 7.14 mg/kg body weight of sildenafil citrate (reference drug), 25, 50 and 100 mg/kg body weight of AEAML once daily for 7 days. Data were analyzed using a one-way Analysis of Variance (ANOVA) and Tukey's post-hoc test at a 5% level of significance after the determination of male sexual behaviour parameters and associated biochemical indices.RESULTSAEAML contained 8 mineral elements and 14 amino acids; potassium (368.24 mg/100g) and glycine (352.70 mg/100g) were the most abundant while cadmium (0.01 mg/100g) and histidine (0.70 mg/100g) were the least. Administration of paroxetine prolonged/increased (p < 0.05) the mount latency (ML), intromission latency (IL), ejaculation latency (EL), post-ejaculatory interval (PEI), and lowered/reduced (p < 0.05) the mount frequency (MF), intromission frequency (IF) and ejaculation frequency (EF). Paroxetine also decreased the weight of the caudal epididymis, seminal vesicle, ventral prostate, and testis, levels of dihydrotestosterone (DHT), testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), dopamine, acetylcholine (ACH), nitric oxide (NO), cyclic guanosine monophosphate (cGMP) and increased the levels of serotonin, γ-aminobutyric acid (GABA), phosphodiesterase V (PDE V) and acetylcholinesterase (AChE) of the animals. In contrast, AEAML significantly (p < 0.05) lowered/reduced the paroxetine-induced related increases in the ML, IL, EL, PEI, and prolonged/increased (p < 0.05) the paroxetine-induced related decreases in the MF, IF and EF. The AEAML also reversed (p < 0.05) the paroxetine-induced related decreases in the weight of the caudal epididymis, seminal vesicle, ventral prostate, testis, levels of DHT, testosterone, LH, FSH, dopamine, ACH, NO, cGMP and the paroxetine-induced related increases in the levels of serotonin, GABA, PDE V and AChE.CONCLUSIONAEAML contains aphrodisiac bioactive agents that can be explored as drug lead for MSD.

103

项与多发性硫酸脂酶缺乏症相关的新闻（医药）

2024-10-24

·生物制品圈

HPV18抗体持久性，四价加卫苗的那条“瘸腿”

四价HPV疫苗（加卫苗）一度成为中国女性的中庸之选——价格适中、年龄友好、价次上档次、货源相对九价更丰富。8月成都所的四价HPV疫苗纳入优先评审程序，也一度成为资本市场进一步唱衰二价的由头。然而近期的几项研究却显示，HPV18型抗体阳性率恐成四价HPV疫苗的阿喀琉斯之踵。近期两项研究带来的担忧 10月6日，刊载于《中华预防医学杂志》的一项评估20~45岁中国女性接种四价人乳头瘤病毒（HPV）疫苗10年保护效果和免疫原性的研究指出，疫苗接种组和补接种组HPV18抗体阳性率分别为35.5%（161/453）和76.0%（149/196），明显低于其他3个型别（ P<0.05）。对于该现象，研究者指出本研究及其他长期随访研究均发现：即使HPV18抗体低于阳性界值，仍未观察到该型别癌前病变或宫颈癌病例，提示目前制订的阳性界值可能高于实际的抗体保护界值，但仍需密切观察疫苗型别相关的宫颈病变。 8月13日，NPJ vaccines发表的一项由瑞典卡罗林斯卡医学院学者发起的队列研究，也复现了该项研究结果类似结论。12年的队列随访研究显示：每7名接种四价疫苗的女性中就有1 名检测不到针对HPV18型的中和抗体和总结合抗体（约14%），而二价总体情况较好。左图为HPV16型、右图为HPV18型总的结合抗体水平，橙色为接种二价、蓝色为接种四价者在评估HPV16/18型血清阴性是否会影响对其他疫苗HPV类型的血清阴性风险时发现：四价疫苗接种者中，与血清阳性者相比，HPV18型中和抗体血清阴性者的HPV16型中和抗体血清阴性风险高出70倍（95% CI 9.3-530）。即如果一位女性HPV18型阴性，那么她HPV16型抗体转阴的可能性更高。四价HPV疫苗的18型抗体不足情况普遍早在2008年的一项研究就提到，接种四价HPV疫苗4年后，有40%的HPV18型抗体下降到无法检测到的水平。而在我国广西省开展的一项研究也有类似发现：随访42个月（3.5年）后，HPV18型cLIA抗体阳性者的比例从峰值时的＞99%快速下降至53.6%（27-45岁人群更是降至37.6%）。 HPV18型抗体阳性率随时间变化：左四价；中国产二价；右进口二价另外两款2价HPV疫苗在国内开展的III期临床研究结果则与上述瑞典学者的研究相似，尽管所用检测方法不一致，但通过阳性率维持情况也可以略作一观：国产二价（Cecolin）随访66个月（5.5年）后的HPV18型血清抗体阳性率从峰值的100%下降至98.3%（其中27-45岁女性98.5%）；进口二价（Cervarix）随访72个月（6年）后HPV18型血清抗体阳性率从峰值的99.6%下降至95.8%。由于国产四价HPV疫苗尚未上市和披露该情况，因此尚不清楚国产四价HPV疫苗是否会出现该情况。当然目前来看，四价似乎已经成为MSD的弃牌转而独宠九价，四价表现如何不再重要。 HPV18型与约10%的宫颈癌相关 HPV18型与全球约10%的宫颈癌病例相关，是全球宫颈癌相关的第二大致癌型别。我国这一比例也相似：在ICO的报告中，与我国约10%的宫颈癌有关（归因TOP2，仅次于HPV16）；国家癌症中心数据显示，HPV18与我国约7.8%的宫颈鳞癌有关；2023年华西附二院一项研究显示（2454例宫颈癌患者），HPV18与6%的鳞癌相关，与29.4%的腺癌相关。而四价HPV疫苗所预防的另外两个HPV6/11型，在国内III期78个月随访中未在对照组观察到由HPV6/11型所致生殖器疣的临床终点，但国外随访3年就出现HPV6/11型所致193例生殖器疣患者，这也进一步体现了国内外HPV基因型的流行差异和疫苗选择差异。 ps：本文仅供交流探讨，不做疫苗接种决策参考。参考资料：潘程浩, 等. 中华预防医学杂志, 2024, 58(10): 1508-1513. Gray P, et al. NPJ Vaccines. 2024 Aug 13;9(1):146. Joura, E. A. et al. Vaccine26, 6844–6851 (2008). Huang T, et al. Vaccine. 2018 Mar 7;36(11):1368-1374. Zhao FH, et al. Lancet Infect Dis. 2022 Dec;22(12):1756-1768. Zhu FC, et al. Cancer Med. 2019 Oct;8(14):6195-6211. Chen W, et al.Cancer Causes Control. 2009 Nov;20(9):1705-13. Tang X, et al. J Med Virol. 2023 Jan;95(1):e28302. Yu YQ, et al. J Cytol. 2022 Oct-Dec;39(4):137-147. 中国尖锐湿疣临床诊疗指南(2021完整版)[J].中国皮肤性病学杂志,2021,35(04):359-374. 魏丽惠,谢幸,刘继红等.中国妇产科临床杂志,2020,21(02):158-162. Vaccine. 2015 Nov 27;33(48):6855-64. 识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

疫苗优先审批临床3期

2024-10-10

·PRNewswire

Merck Manuals: What Travelers Need to Know About Dengue

RAHWAY, N.J., Oct. 10, 2024 /PRNewswire/ -- Dengue fever is a mosquito-borne viral infection that when mild, can cause flu-like symptoms. But in a more severe form, the virus can also lead to internal bleeding, organ damage, and death. For individuals living or traveling where dengue is common, there are important things to know to minimize your risk. In a new editorial from MerckManuals.com, Thomas M. Yuill, PhD, University of Wisconsin-Madison, shares information and advice. 1. Not all mosquitoes carry dengue Dengue is spread to people through the bites of infected Aedes species mosquitoes, says Yuill. Each year, about 50 to 100 million cases of dengue and about 20,000 deaths occur worldwide. However, in the United States, only about 100 to 200 cases occur annually, with nearly all brought in by travelers returning from other countries, says Yuill. 2. Dengue is spreading to new areas Dengue is common in the tropics and subtropics worldwide. It is often found in Southeast Asia but has become more prevalent in recent years in Central and South America, including countries like Brazil. At the same time, Aedes mosquitoes are turning up in new places due to human activity and a changing climate. In the United States, they've been found in states including Florida, Southern California, Texas, Arizona and the Midwest. A few cases of locally transmitted dengue have occurred in Hawaii, Florida and Texas. 3. Dengue comes in three phases Dengue symptoms typically begin suddenly, causing fever, chills, a severe headache, pain when the eyes are moved, extreme fatigue and severe generalized body aches, particularly in the back, legs, and joints. These symptoms typically last for a few days, after which patients begin to feel better for about 24 hours. "People may think they're out of the woods, but then the fever can return, along with more serious effects, including dengue hemorrhagic fever, bleeding and shock," says Yuill. 4. Dengue is not contagious In a vast majority of instances, people with dengue cannot transmit it to others, says Yuill. A mosquito can transmit it by biting a person with an infection and then biting someone else. Although uncommon, a pregnant woman can pass the dengue virus to her fetus during pregnancy or around the time of birth. 5. There is currently no vaccine against new cases The only dengue vaccine currently available in the United States is approved for children who have been previously infected and live in an area where the disease is common, says Yuill. There are a number of vaccines in development that can be used for individuals who have not had prior dengue infections as well as those who have. 6. Travelers need to take precautions Anyone traveling to parts of the world where dengue is common should take steps to protect themselves and their fellow travelers. "When traveling, the same best practices around avoiding all mosquito bites apply," says Yuill. Wear light-colored, long-sleeved, loose-fitting clothing. Use insect repellant. Some repellants are increasingly being added to sunscreens. Just be sure to check the labels before using any product on children. 7. Travelers should watch for symptoms Symptoms of dengue typically begin about three to 15 days after being bitten by an infected mosquito. Often, a traveler only starts to feel sick after they return home. If you've traveled to an area where dengue is present and start to feel sick, it's essential to provide travel details when talking to your doctor, says Yuill. To read more of Yuill's insights on dengue, visit this editorial on MerckManuals.com. About The Merck Manuals and MSD Manuals First published in 1899 as a small reference book for physicians and pharmacists, The Merck Manual grew in size and scope to become one of the world's most widely used comprehensive medical resources for professionals and consumers. As The Manual evolved, it continually expanded the reach and depth of its offerings to reflect the mission of providing the best medical information to a wide cross-section of users, including medical professionals and students, veterinarians and veterinary students, and consumers. In 2015, The Manuals kicked off Global Medical Knowledge 2020, a global initiative with the goal to make the best current medical information accessible by up to three billion professionals and patients around the world by 2020. The Manuals achieved that goal, and today its medical information is available in nearly 250 countries and in 14 languages. It's continuing its ambitious mission through outreach, education and creating new reliable medical resources. For access to thousands of medical topics with images, videos and a constantly expanding set of resources, visit MerckManuals.com or MSDManuals.com and connect with us on social media: For Consumers in the U.S. and its territories: X (formerly Twitter) and Facebook. For Professionals in the U.S. and its territories: X (formerly Twitter) and Facebook About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. SOURCE The Merck Manuals WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

疫苗上市批准

2024-09-25

·生物制品圈

体外转录(IVT) mRNA再次牵手热门领域——PROTAC疗法

导读：基于“事件驱动”的药理学，蛋白水解靶向嵌合体（PROTAC）技术借助泛素-蛋白酶体系统（UPS）可以实现“不可成药”目标蛋白（POI）的降解，是药物开发的新兴技术。然而，当前在研的PROTAC技术主要有小分子药物和重组蛋白（bioPROTAC）两种类型。其中小分子药物存在靶蛋白结合部分优化异常困难的挑战，而重组蛋白面临着膜渗透性差等难题随着体外转录（IVT）mRNA和脂质纳米颗粒（LNP）技术的成熟和广泛应用，目前PROTAC的研究方向也采纳了IVT mRNA技术。本期文章，菌菌汇总了IVT mRNA-LNP技术在热门领域PROTAC疗法中的应用潜能。 01 mRNA PROTAC靶向PCNA 题目：Targeted degradation of PCNA outperforms stoichiometric inhibition to result in programed cell death 作者：默沙东（MSD）药物研发团队期刊： Cell Chemical Biology（IF: 6.6）链接： https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/36318925/ 靶点介绍：他们选择增殖细胞核抗原（PCNA）这一肿瘤靶点。PCNA在DNA复制和细胞增殖中发挥关键作用。抑制PCNA能够使肿瘤细胞对化疗敏感，因此被认为是一种广谱抗肿瘤靶点。早期，MSD研发团队开发了靶向PCNA的bioPROTAC平台Con1-SPOP。Con1-SPOP是一种由靶点蛋白结合域和 E3 连接酶组成的融合蛋白，能够有效降解靶蛋白。该候选药物面临的主要挑战是药物递送问题。研究方法：本次研究由MSD多个药物研发部门合作在Cell Chemical Biology发表。他们尝试利用LNP递送Con1-SPOP mRNA并通过体内外试验评估了其作用效果。Con1-SPOP mRNA的制备过程包括质粒模板制备、体外转录（IVT）、LNP包封。研究通过细胞凋亡试验、蛋白组分析、流式分析、小鼠异种移植模型评估Con1-SPOP mRNA的抑制活性。研究结果：研究人员通过体内和体外试验表明，PCNA降解导致DNA损伤、p53激活和细胞凋亡，且PCNA的降解在整体蛋白质组学特征与PCNA抑制方面有所不同。PCNA在体内的降解导致肿瘤生长完全被抑制。整体而言，脂质纳米颗粒递送mRNA bioPROTAC分子能够快速降解PCNA蛋白。图示基于mRNA的bioPROTAC平台 02 mRNA PROTAC靶向ERα与BCL-xL 题目：mRNA PROTACs: engineering PROTACs for high-efficiency targeted protein degradation 作者：清华大学深圳国际研究生院谭英课题组期刊：MedComm (2020) （IF: 10.7）链接：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/38374873/ 靶点介绍：研究使用了两个靶蛋白验证mRNA PROTAC（m-PROTAC）的适用性：雌激素受体 α （ERα）和 B 细胞超大淋巴瘤蛋白（BCL-xL）。ERα在大多数类型的乳腺癌细胞中过表达，是乳腺癌治疗的一个重要靶点。BCL-xL是一种抗凋亡蛋白，在多种癌症细胞中过表达，是抗癌治疗的关键靶点。研究方法：研究中mRNA PROTAC同样编码靶点蛋白结合域（配体）和 E3 连接酶组成的融合蛋白，其中ERα涉及了两个配体序列，通过Linker（GSGS）连接，同时在上游添加了eGFP和P2A作为报告序列。图示基于mRNA的bioPROTAC平台研究结果：体外实验表明，m-PROTACs 可以成功降解不同细胞系中的靶蛋白，并且比传统的 p-PROTACs 更有效地抑制细胞增殖。体内实验表明，m-PROTAC 处理导致 4T1 小鼠异种移植模型中的肿瘤显著消退。 03 mRNA PROTAC靶向KRAS蛋白题目：Lipid-mediated intracellular delivery of recombinant bioPROTACs for the rapid degradation of undruggable proteins 作者：宾夕法尼亚大学Andrew Tsourkas课题组期刊：Nature Communications （IF: 14.7）链接：https://pubmed-ncbi-nlm-nih-gov.libproxy1.nus.edu.sg/38987546/ 这项研究的初衷是解决bioPROTAC递送的难题，他们基于LNP递送平台，开发了一种模块化的重组bioPROTAC平台。其一是优化的bioPROTAC蛋白组成，包括三种必须元素：N 端 E3连接酶IpaH9.8、靶点蛋白结合配体DARPin和C 端的阴离子多肽标签ApP。其二是优化的LNP递送系统，在常规的可电离脂质（C12-200）、辅助磷脂DOPE、胆固醇、PEG脂质四组分LNP的基础上，添加了另一种阳离子脂质DOTAP，且磷脂占比大幅提高。这项研究中使用了bioPROTAC mRNA作为阳性对照，表明其在靶蛋白降解和肿瘤细胞抑制效应方面的作用与重组bioPROTAC类似，而蛋白质组学分析显示部分差异。图示基于蛋白的bioPROTAC平台 04 circRNA PROTAC靶向PCNA 题目：Circular mRNA encoded PROTAC (RiboPROTAC) as a new platform for the degradation of intracellular therapeutic targets 作者：苏州科锐迈德研发团队期刊：bioRxiv预印本链接：https://www.biorxiv.org/content/10.1101/2022.04.22.489232v1 靶点介绍：科锐迈德同样选择了一种广谱抗肿瘤靶点——增殖细胞核抗原（PCNA），这一点与上文中默沙东团队的选择一致。研究方法：科锐迈德团队使用了一种特殊结构的IVT mRNA——环状RNA（circRNA）编码 bioPROTAC 蛋白质降解剂，他们在文章中将其命名为RiboPROTAC。circRNA的制备步骤包括：质粒（IVT模板）合成、IVT反应、DNase I消化和HPLC纯化。circRNA的IVT模板序列包含PIE 元件、IRES、编码区等必要元件，其中编码区域由 PCNA 结合肽、柔性接头和 E3 连接酶 SPOP167-374 组成。研究通过细胞增殖实验、小鼠异种移植模型评估了PROTAC mRNA的抑制活性。研究结果：使用RiboPROTAC转染细胞后，高达75%的目的蛋白被降解。癌细胞系 B16F10 和 A549中PCNA蛋白水平降低，而且细胞增殖受到强烈抑制、细胞凋亡率增高、细胞周期停滞。体外结果表明RiboPROTAC 通过降解PCNA抑制癌细胞的增殖。小鼠体内实验表明，编码 PCNA 靶向降解剂的circRNA表现出显著的肿瘤抑制作用。图示基于circRNA的RiboPROTAC平台 05 总结蛋白水解靶向嵌合体（PROTAC）技术是一种新的治疗模式，通过将E3泛素连接酶受体工程募集到目标蛋白，诱导目标蛋白的多泛素化和降解，从而消耗“有害”蛋白，达到治疗疾病的目的。 mRNA介导的PROTAC策略整合了PROTAC蛋白和IVT-mRNA技术的优势： 1)相比RNAi等技术，bioPROTAC能够识别特定构象或翻译后修饰的蛋白，完全根除蛋白质及其相关的生物学功能； 2)相比小分子介导的PROTAC疗法，mRNA PROTAC具有更好的生物相容性、选择性和安全性，且具有更低的剂量和更好的催化性质； 3)相比蛋白介导的PROTAC疗法，mRNA及其LNP递送系统的安全性已在大规模人群中得到了验证，能够避免PROTAC蛋白的递送问题。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

信使RNA蛋白降解靶向嵌合体