CAREER: Photoactivated miRNA delivery for modulation of human adipose stromal cell differentiation

1254281 Hayes用微小RNA（miRNA）调节细胞和组织功能是一种有前途的技术，可改善伤口愈合和组织修复过程的控制，微小RNA是在动物和植物组织中天然发现的小的非编码RNA序列。当与成人干/基质细胞（ASC）疗法相结合时，这些技术可能会导致一种新的再生医学范式。几种基于miRNA和其他潜在的寡核苷酸的治疗剂已被证明具有潜在的生物活性，但由于毒性和缺乏特异性作用，目前最先进的寡核苷酸递送技术在很大程度上与临床治疗不相容。 该项目将解决对临床相关的，安全有效的miRNA递送系统的迫切需求，该系统在患病或受损组织的部位提供时间和空间控制。作为一个主要目标，该项目将优化，纳米粒子（NP）为基础的，光激活的，miRNA传递系统（LAMD）的光激活的空间和时间的骨和血管形成的调控使用ASC作为模型系统。第二个目标是开发一种成本效益更高、性能更强的LAMD系统制造工艺。 研究生产过程中提高产量和形态控制将解决一个关键的限制使用靶向粒子治疗的发展。随着寿命的延长和增加活动水平的老龄化人口，我们预计将看到一个大幅度增加的人数与骨科损伤的病人。特别感兴趣的是骨骼疾病的解决方案，例如骨不愈合和不愈合，由磨损、癌症、创伤或关节置换引起的临界尺寸缺陷。开发一种光活化的、基于纳米颗粒的miRNA递送系统，该系统解决了传统miRNA递送载体的局限性，同时提供对活性的空间和时间控制，这对于miRNA在再生医学中的应用可能是变革性的。该项目将提供直接支持，每年有几个本科生和研究生在这个项目上工作的研究学者。该项目为生物医学工程，化学及相关领域的学生提供了一个独特的跨学科机会，以建立纳米材料合成，干细胞生物学，光生物学和再生医学领域的基础知识和欣赏。该项目的外联部分将包括K-12、本科生和研究生教育活动。

1254281HayesModulation of cell and tissue function with microRNA (miRNA), which are small non-coding RNA sequences naturally found in animal and plant tissues, is a promising technique to improve the control of wound healing and tissue repair processes. When combined with adult stem/stromal cell (ASC) therapies these techniques may result in a new regenerative medicine paradigm. Several miRNA and other potential oligonucleotide based therapeutics have been demonstrated to posses potent bioactivity but current state-of-the-art oligonucleotide delivery techniques are largely incompatible with clinical therapies due to toxicity and lack of specific action. This project will address the critical need for a clinically relevant, safe and effective miRNA delivery system which provides temporal and spatial control of activation at the site of diseased or damaged tissue. As a primary objective the project will optimize, a nanoparticle (NP) based, light activated, miRNA delivery system (LAMD) for the light activated spatial and temporal regulation of bone and blood vessel formation using ASC as a model system. A secondary objective is the development of a more cost effective and robust processes for the fabrication of a targeted version of the basic LAMD system. Research into manufacturing processes with improved yields and morphological control will address a critical limitation to the development of therapies using targeted particles.With the lengthening life span and increasing activity levels of the aging population we expect to see a substantial increase in the number of patients presenting with orthopaedic injuries. Of particular interest are solutions to skeletal disorders, such as bone disunions and non-healing, critical sized defects caused by wear, cancers, trauma or as the result joint replacement. The development of a photoactivated, nanoparticle based, miRNA delivery system that addresses the limitations of traditional miRNA delivery vectors while providing for spatial and temporal control of activity could be transformative for miRNA use in regenerative medicine. This project will provide direct support for several undergraduate and graduate students per year to work on this project as research scholars. The project presents a unique and interdisciplinary opportunity for students majoring in biomedical engineering, chemistry and related fields to build fundamental knowledge and appreciation in the areas of nanomaterial synthesis, stem cell biology, photobiology and regenerative medicine. The outreach components of this project will include K-12, undergraduate and graduate education activities.