BC-mediated delivery of thromboprophylaxis

BC 介导的血栓预防

基本信息

  • 批准号:
    10475755
  • 负责人:
  • 金额:
    $ 66.66万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-01 至 2025-06-30
  • 项目状态:
    未结题

项目摘要

No anti-thrombotic agent (ATA) is safe and effective in the many patients at a combined risk of acute thrombosis and bleeding, e.g., in the early post-surgery period. To address this unmet need, we develop drug delivery systems (DDS) executing two main functions: A) Block access of ATA to off- target sites, e.g., hemostatic plugs formed after surgery, while B) Optimize pharmacokinetics and deliver ATA into subsequent thrombi, where ATA is activated by thrombin. ATA fused with single- chain fragments (scFv) targeted to red blood cells (RBC) bind to these carriers that execute dual blocking/delivering function. Proof-of-concept is emerging in models of pre-existing and nascent clots in animals. Here we devise humanized scFv/ATA targeted to human RBC and will test them in a humanized microfluidic system (HMF), in transgenic (TG) mice expressing humanized target epitopes on blood cells, and in the perfusion of isolated human lungs. We will pursue three aims. Aim 1. RBC loading. We will characterize scFv/ATA loading onto RBC: A) Binding (copies/cell, on/off kinetics); B) Effect on RBC functionality, biocompatibility and biomechanics; and, B) Regulation of distribution of scFv/ATA between RBC in circulation. We also will characterize biomechanical factors modulating RBC/ATA delivery and effect on clot dynamics and structure, in particular, impact of RBC rigidification, caused by either drug loading or by intrinsic pathophysiological changes in patient's blood. Aim 2. Mechanistic insights. We will interrogate previously unrecognized yet critically aspects of the RBC/ATA workings, in particular their interaction with vascular endothelium and transfer of the drug cargo to these and other vascular cells. In this Aim we will use standard mouse in vivo models, microfluidic model and perfusion of isolated human lungs model. Aim 3. Appraisal of benefit/risk ratio. We are developing TM mice expressing human RBC determinants in mouse EBC, in order to study scFv/ATA loaded on "human RBC" in vivo: A) PK/BD, complement activation, phagocyte uptake and vascular adhesion of RBC/ATA in TG mice; B) Define the time window/extent of anti-thrombotic effect of human RBC/ATA in models of arterial vs venous thrombosis in TG mice; B) Affirm the safety of RBC/ATA. We will detect adversities of scFv/ATA including abnormalities of RBC. To defuse potential issues, if necessary, we will use more benign loading regimen. Together, these studies will advance mechanistic insights and clinical translation of a novel way to mitigate thrombosis in currently unprotected patients by providing a new and tractable approach to understanding thrombus development and a rational approach to deliver cell-directed therapeutics
没有抗血栓药物(ATA)是安全有效的许多患者在合并风险

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Vladimir R Muzykantov其他文献

Vladimir R Muzykantov的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Vladimir R Muzykantov', 18)}}的其他基金

BC-mediated delivery of thromboprophylaxis
BC 介导的血栓预防
  • 批准号:
    10277205
  • 财政年份:
    2021
  • 资助金额:
    $ 66.66万
  • 项目类别:
Dual drug delivery to lung/blood interface in respiratory infections.
在呼吸道感染中向肺/血液界面双重给药。
  • 批准号:
    10179690
  • 财政年份:
    2021
  • 资助金额:
    $ 66.66万
  • 项目类别:
Dual drug delivery to lung/blood interface in respiratory infections.
在呼吸道感染中向肺/血液界面双重给药。
  • 批准号:
    10614476
  • 财政年份:
    2021
  • 资助金额:
    $ 66.66万
  • 项目类别:
Dual drug delivery to lung/blood interface in respiratory infections.
在呼吸道感染中向肺/血液界面双重给药。
  • 批准号:
    10393610
  • 财政年份:
    2021
  • 资助金额:
    $ 66.66万
  • 项目类别:
BC-mediated delivery of thromboprophylaxis
BC 介导的血栓预防
  • 批准号:
    10652489
  • 财政年份:
    2021
  • 资助金额:
    $ 66.66万
  • 项目类别:
Vascular Targeting of Nanocarriers for RNA
RNA 纳米载体的血管靶向
  • 批准号:
    10343691
  • 财政年份:
    2021
  • 资助金额:
    $ 66.66万
  • 项目类别:
Vascular Targeting of Nanocarriers for RNA
RNA 纳米载体的血管靶向
  • 批准号:
    10093767
  • 财政年份:
    2021
  • 资助金额:
    $ 66.66万
  • 项目类别:
Vascular Targeting of Nanocarriers for RNA
RNA 纳米载体的血管靶向
  • 批准号:
    10560629
  • 财政年份:
    2021
  • 资助金额:
    $ 66.66万
  • 项目类别:
Vascular delivery of nanocarriers by erythrocyres
红细胞对纳米载体的血管输送
  • 批准号:
    9922385
  • 财政年份:
    2018
  • 资助金额:
    $ 66.66万
  • 项目类别:
Vascular delivery of nanocarriers by erythrocyres
红细胞对纳米载体的血管输送
  • 批准号:
    10153877
  • 财政年份:
    2018
  • 资助金额:
    $ 66.66万
  • 项目类别:

相似海外基金

Acute senescence: a novel host defence counteracting typhoidal Salmonella
急性衰老:对抗伤寒沙门氏菌的新型宿主防御
  • 批准号:
    MR/X02329X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Fellowship
Transcriptional assessment of haematopoietic differentiation to risk-stratify acute lymphoblastic leukaemia
造血分化的转录评估对急性淋巴细胞白血病的风险分层
  • 批准号:
    MR/Y009568/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Fellowship
Combining two unique AI platforms for the discovery of novel genetic therapeutic targets & preclinical validation of synthetic biomolecules to treat Acute myeloid leukaemia (AML).
结合两个独特的人工智能平台来发现新的基因治疗靶点
  • 批准号:
    10090332
  • 财政年份:
    2024
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Collaborative R&D
Cellular Neuroinflammation in Acute Brain Injury
急性脑损伤中的细胞神经炎症
  • 批准号:
    MR/X021882/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Research Grant
STTR Phase I: Non-invasive focused ultrasound treatment to modulate the immune system for acute and chronic kidney rejection
STTR 第一期:非侵入性聚焦超声治疗调节免疫系统以治疗急性和慢性肾排斥
  • 批准号:
    2312694
  • 财政年份:
    2024
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Standard Grant
Combining Mechanistic Modelling with Machine Learning for Diagnosis of Acute Respiratory Distress Syndrome
机械建模与机器学习相结合诊断急性呼吸窘迫综合征
  • 批准号:
    EP/Y003527/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Research Grant
FITEAML: Functional Interrogation of Transposable Elements in Acute Myeloid Leukaemia
FITEAML:急性髓系白血病转座元件的功能研究
  • 批准号:
    EP/Y030338/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Research Grant
KAT2A PROTACs targetting the differentiation of blasts and leukemic stem cells for the treatment of Acute Myeloid Leukaemia
KAT2A PROTAC 靶向原始细胞和白血病干细胞的分化,用于治疗急性髓系白血病
  • 批准号:
    MR/X029557/1
  • 财政年份:
    2024
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Research Grant
ロボット支援肝切除術は真に低侵襲なのか?acute phaseに着目して
机器人辅助肝切除术真的是微创吗?
  • 批准号:
    24K19395
  • 财政年份:
    2024
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Collaborative Research: Changes and Impact of Right Ventricle Viscoelasticity Under Acute Stress and Chronic Pulmonary Hypertension
合作研究:急性应激和慢性肺动脉高压下右心室粘弹性的变化和影响
  • 批准号:
    2244994
  • 财政年份:
    2023
  • 资助金额:
    $ 66.66万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了