MicroRNA and drug delivery

Joseph S. Fernandez-Moure, Jeffrey Van Eps, Bradley K. Weiner, Mauro Ferrari, Ennio Tasciotti

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The human genome was once thought to be a redundant sequence containing few functional regions coding for proteins. This teaching is being rewritten as we continue to understand the vast complexity of the noncoding regions of the genetic code. These regions we now understand are transcribed into small single-stranded segments or microRNAs (miRNAs) that participate in the regulation of gene expression. miRNAs interact across many pathways and thus have the potential as targets for oncologic therapies. Their efficacy is limited because methods to traverse the many biologic barriers are yet to be developed. In order to achieve effective therapeutic levels at the site of interest, the tumor, the miRNA must be shuttled to the site and simultaneously be protected from the body's defensive mechanisms. To this end, scientists have developed many vehicles for delivery at both the micro- and nanoscale using both synthetic and biologically derived vectors. Viral vectors continue to be the most commonly used vehicles, but are plagued by complications related to the vector itself. These inadequacies led researchers to explore synthetic materials such aspolylactic co-glycolic-acid (PLGA), silicon, gold, and liposomes to overcome the biobarriers of our body. While these vehicles have shown promise, problems such as high clearance rates, poor tumor accumulation and targeting, and adverse reactions have limited their translation into the clinic. In order to overcome these problems, a multistage theory was developed. By decoupling the tasks required of the carrier system, the multistage delivery system is able to simultaneously protect the payload, target the site of interest, and deliver the payload in therapeutic concentrations. This presents a paradigm shift in the concept of drug delivery and may provide the solution to the limited translational gene therapy in oncology.

Original languageEnglish (US)
Title of host publicationMicroRNA in Development and in the Progression of Cancer
PublisherSpringer New York
Pages359-403
Number of pages45
ISBN (Electronic)9781489980656
ISBN (Print)1489980644, 9781489980649
DOIs
StatePublished - Jan 1 2014

Keywords

  • Drug delivery
  • Liposomes
  • Multistage delivery
  • Nanoparticles
  • Nanotechnology
  • Silicon
  • Viral vector
  • miRNA

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    Fernandez-Moure, J. S., Van Eps, J., Weiner, B. K., Ferrari, M., & Tasciotti, E. (2014). MicroRNA and drug delivery. In MicroRNA in Development and in the Progression of Cancer (pp. 359-403). Springer New York. https://doi.org/10.1007/978-1-4899-8065-6_19