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Altering Long non-coding RNA (LncRNA) Expression: Edjah Nduom While repurposing immune therapy and other drugs has proven to be effective in some cancers, this approach has not proven viable for treating glioblastoma and pediatric cancers including medulloblastoma and gliomas. What if there was a way to alter the immune cells in our brain to make them more receptive to immune therapy? Dr. Nduom believes that the answer lies in developing a novel class of drugs to target Long non-coding RNA (LncRNA). Genetic sequencing has resulted in discoveries about DNA and the messenger RNA responsible for encoding proteins, but there is a much larger part of the human genome uninvolved in coding genes. The term non-coding RNA (ncRNA) is a commonly employed term for RNA that does not encode a protein, but this does not mean that such RNAs do not contain information nor have function. Although it has been generally assumed that most genetic information is transacted by proteins, recent evidence suggests that the majority of the genome is in fact transcribed into ncRNAs, many of which are alternatively spliced and/or processed into smaller products. Dr. Nduom is now interested in exploring tens of thousands of longer transcripts called LncRNAs, which is largely uncharted territory for brain tumor research, and developing a new class of drugs to alter them. As he has been characterizing these molecules, Dr. Nduom’s team has data to suggest that the LncRNAs are different in brain tumor patients than in healthy volunteers. Dr. Nduom is finding that LncRNAs are very specific (they might be upregulated in immune cells but not in brain cells or muscle cells, for example), and they have different functions in different types of cells, as well. Moreover, LncRNAs perform their functions despite being present in only a few transcripts per cell. That is to say, just the slightest presence of LncRNA can change the entire function of a cell. Similarly, it does not take a lot to knock down a LncRNA that may be causing problems. And, because they are easy to knock down, LncRNAs might be ideal therapeutic targets. In partnership with Hui Mao, PhD, a nanoparticle expert at Emory, Dr. Nduom wishes to undertake a pilot study to develop a whole new class of therapeutics to target the LncRNAs and make immune therapy effective in glioblastoma. The research team hopes to design nanoparticles small enough to cross the blood brain barrier to target the aberrant LncRNAs in immune cells and macrophages most frequently immune suppressed in glioblastoma. Dr. Nduom’s team believes this approach could render immune therapy effective in glioblastoma for the first time.

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