NanoScript Can Activate or Deactivate Specific Genes for Non-Viral Stem Cell Differentiation


While stem cell therapies appear very promising, there is a critical gap that exists between our current knowledge and the practical application of stem cell therapies, and as a result, there is not a single stem cell therapy that is approved by the FDA! Hence, there is currently an urgent demand by stem cell scientists and clinicians for an alternative platform that induces stem cell differentiation in an efficient, non-viral manner which is safe for potential translation into the clinic for treatment of debilitating diseases. This this end, we have spent the past 5 years to develop a bio-inspired platform that can non-virally regulate genes in stem cells to induce their differentiation.

Sahishnu Patel, a graduate student in Prof. KiBum Lee’s research group (Rutgers University), developed a novel platform called NanoScript, which is a nanoparticle-based replica of transcription factors. Transcription factors (TFs) are proteins that regulate gene expression and stem cell differentiation. NanoScript is comprised of functional biomolecules, which mimic specific domains of transcription factor proteins, assembled on a nanoparticle core. This simple, yet precise design enables NanoScript to replicate the structure and function of TF proteins. As a result, NanoScript can non-virally regulate genes in stem cells to induce their differentiation into any desired cellular lineage (i.e. neurons, muscle, cartilage, etc.).

Specifically, we recently designed NanoScript to regulate muscle cell differentiation by targeting myogenic regulatory factors (MRFs), which play an important role in inducing myogenesis. This NanoScript-MRF is stable in physiological environments, localizes within the nucleus, induces differentiation of adipose-derived mesenchymal stem cells into mature muscle cells in 7 days, and is naturally excreted from induced muscle cells. This research was recently published in ACS Nano and highlighted by 13 scientific news organizations worldwide.

The tunable and interchangeable biomolecules of NanoScript can easily be modified to either activate or deactivate any gene of interest. Specifically, in a follow-up demonstration, NanoScript was redesigned to mimic the function of transcription repressor proteins to downregulate gene expression for enhancing stem cell differentiation. First, we show a proof-of-concept demonstration using a GFP-specific NanoScript to knockdown GFP expression in neural stem cells (NSCs). Then, we show that a Sox9-specific NanoScript can repress Sox9 expression to initiate enhanced differentiation of NSCs into functional neurons. Overall, the tunable properties and gene knockdown capabilities of NanoScript enables its utilization for gene-repression applications in stem cell biology.

This powerful feature of NanoScript—of being able to upregulate or downregulate any desired gene, including genes involved in stem cell differentiation—makes NanoScript a powerful research tool for stem cell scientists. Moreover, the ability of NanoScript to regulate these genes in a non-viral manner without leaving a genetic or physical footprint on the cells is a feature highly desired by stem cell clinicians, and hence, holds potential for use in stem cell-based therapies.

  1. Patel, S.; Yin, P. T.; Sugiyama, H.; Lee, K.-B. Inducing Stem Cell Myogenesis Using NanoScript. ACS Nano 2015, 9, 6909.
  2. Patel, S.; Dean Chueng, S.-T.; Yin, P.; Dardir, K.; Song, Z.; Pasquale, N; Kwan, K.; Sugiyama, H.; Lee, K.-B. Induction of Stem Cell-Derived Functional Neurons via NanoScript-based Gene Repression. Angewandte Chemie 2015, (Accepted)

Links to Research Highlighted in News Outlets:

Group Members: 
Prof. KiBum Lee
Prof. KiBum Lee
Sahishnu Patel
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