SMART NANPs: new molecular platform for communication with human immune system and modulation of therapeutic responses

SMART NANP:与人体免疫系统通讯和调节治疗反应的新分子平台

基本信息

  • 批准号:
    10557793
  • 负责人:
  • 金额:
    $ 38.48万
  • 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:
    2021-02-01 至 2026-01-31
  • 项目状态:
    未结题

项目摘要

Principal Investigator/Program Director (Last, First, Middle): Afonin, Kirill, A PROJECT SUMMARY What if healthcare providers were equipped with biocompatible, biodegradable, robust, and affordable treatment options that combine therapeutic modalities with controlled mechanisms of action? What if this versatile technology had learning capacity and could be educated to recognize patient-specific diseases and interfere with their progression by redirecting fundamental cellular processes? What if the very same formulation could offer an additional means of control over patients’ immune responses and further advance favorable therapeutic outcomes with minimal toxicities? These next generation therapies would then become a game changer in helping to prevent, detect, diagnose, and treat diseases and disabilities at their source. With the support from MIRA (R35) funding, we envision a data-driven platform, SMART NANPs (specific, modular, adjustable, reproducible, and targeted nucleic acid nanoparticles), encoded by self-assembling nucleic acids. By controlling the flow of genetic information across all forms of life, nucleic acids have become instrumental in acquiring new knowledge about major cellular processes and origins of diseases. Besides their diverse biological roles, these biopolymers can be programmed into NANPs with specified physicochemical properties and functionalities that dictate NANPs’ biological actions with endless possibilities for reprogramming cellular behavior through molecular signaling. We recently discovered that different architectural parameters and compositions of NANPs, delivered to primary human immune cells, can activate monocytes and dendritic cells to produce type I and type III interferons. This pioneering work on NANPs’ immunorecognition highlighted an unforeseen clinical application for this technology in the field of vaccines and immunotherapy. A defined structure-function relationship for any given NANP would then allow conditional actuation of its immunorecognition or any other therapeutic activity through a set of embedded architectural codes. With this notion, we introduced two orthogonal concepts of therapeutic NANPs which can be conditionally activated in human cancer cells to release pre-programmed therapeutics. By uniting these breakthroughs and other preliminary findings from my lab, as highlighted in the current application, and integrating them into a unified network of SMART NANPs with programmable control of biodistribution, immunological activity, and therapeutic modules, we will advance the current repertoire of therapies against infectious diseases and cancers (through NANP-based vaccines and immunotherapies), cardiovascular diseases (through regulated coagulation by thrombin-targeting NANPs), and address drug overdose and safety issues (through the biodegradable nature of NANPs and their controlled deactivation). To maximize the successful translation of this technology, the proposed program will employ a multidisciplinary approach that spans the fields of nucleic acid nanotechnology, immunology, drug delivery, translational oncology, and machine learning. The long-term goal of this program is to elevate SMART NANPs to the level of clinical use.
首席调查员/计划主管(最后,第一,中间):Afonin,Kirill, 项目摘要 如果医疗保健提供者配备了生物相容性,可生物降解,健壮且负担得起的 将治疗方式与受控机制相结合的治疗选择?如果这个怎么办 多功能技术具有学习能力,可以接受教育以识别患者特异性疾病和 通过重定向基本的细胞过程来干扰它们的进展?如果非常相同的公式该怎么办 可以提供对患者免疫反应的额外控制手段,并进一步提高有利 毒性最小的治疗结果?这些下一代疗法将成为游戏 改变了帮助预防,检测,诊断和治疗其来源的疾病和疾病的人。与 Mira(R35)资助的支持,我们设想一个数据驱动的平台,智能NANP(特定,模块化, 可调节,可重现和靶向核酸纳米颗粒),由自组装核酸编码。经过 控制各种生命形式的遗传信息的流动,核酸已在 获取有关主要细胞过程和疾病起源的新知识。除了它们多样的生物学 角色,这些生物聚合物可以用指定的物理特性编程到NANP,并且 决定Nanps的生物学作用的功能,具有无限的可能性来重编程细胞 通过分子信号传导行为。我们最近发现不同的建筑参数和 Nanps的组成,递送到原代人免疫力中,可以激活单核细胞和树突状细胞 产生I型和III型干扰素。这项关于Nanps免疫识别的开创性工作突出了 该技术在疫苗和免疫疗法领域的临床应用不可预见。定义 任何给定NANP的结构功能关系将允许其有条件的行动 通过一组嵌入式建筑代码,免疫识别或任何其他治疗活动。与此 概念,我们引入了两个正交的理论nanps概念,可以在 人类癌细胞释放预先编程的治疗。通过团结这些突破和其他 如当前应用程序中突出显示的,我的实验室的初步发现,并将其集成到统一中 智能NANP的网络,可编程控制生物分布,免疫活动和治疗 模块,我们将推动目前针对传染病和癌症的疗法曲目(通过 基于NANP的疫苗和免疫疗法),心血管疾病(通过受调节的凝结 靶向凝血酶的Nanps),并解决药物过量和安全问题(通过可生物降解的性质 Nanps及其受控停用)。为了最大化这项技术的成功翻译, 拟议的计划将采用一种跨学科方法,该方法跨越核酸纳米技术领域, 免疫学,药物输送,翻译肿瘤学和机器学习。该计划的长期目标是 将智能Nanps提升到临床使用水平。

项目成果

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Kirill A Afonin其他文献

Kirill A Afonin的其他文献

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{{ truncateString('Kirill A Afonin', 18)}}的其他基金

Multiplexed electronic counting of scarce protein targets using nucleic acid nanoparticles
使用核酸纳米粒子对稀有蛋白质靶标进行多重电子计数
  • 批准号:
    10353490
  • 财政年份:
    2022
  • 资助金额:
    $ 38.48万
  • 项目类别:
Multiplexed electronic counting of scarce protein targets using nucleic acid nanoparticles
使用核酸纳米粒子对稀有蛋白质靶标进行多重电子计数
  • 批准号:
    10611370
  • 财政年份:
    2022
  • 资助金额:
    $ 38.48万
  • 项目类别:
SMART NANPs: new molecular platform for communication with human immune system and modulation of therapeutic responses
SMART NANP:与人体免疫系统通讯和调节治疗反应的新分子平台
  • 批准号:
    10331771
  • 财政年份:
    2021
  • 资助金额:
    $ 38.48万
  • 项目类别:
Administrative Supplement to SMART NANPs: new molecular platform for communication with human immune system and modulation of therapeutic responses
SMART NANP 的行政补充:用于与人体免疫系统沟通和调节治疗反应的新分子平台
  • 批准号:
    10798083
  • 财政年份:
    2021
  • 资助金额:
    $ 38.48万
  • 项目类别:
Characterization of various multifunctional nucleic acid nanoparticles and understanding their immunotoxicity
各种多功能核酸纳米粒子的表征并了解其免疫毒性
  • 批准号:
    10013239
  • 财政年份:
    2017
  • 资助金额:
    $ 38.48万
  • 项目类别:
Characterization of various multifunctional nucleic acid nanoparticles and understanding their immunotoxicity
各种多功能核酸纳米粒子的表征并了解其免疫毒性
  • 批准号:
    9384048
  • 财政年份:
    2017
  • 资助金额:
    $ 38.48万
  • 项目类别:

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