• Aim 1: Creation and Screening of Novel saRNAs
  • In collaboration with the KRIBB team, we plan to design and synthesize 20 groundbreaking saRNA plasmid DNA constructs.
  • Leveraging our in-house IVT protocol, we will produce the desired RNA.
  • Each construct will be endowed with a unique barcode for identification, strategically placed upstream of the 3’ UTR and polyA tail.
  • We will subject the constructs to various human culture cells and, using high-throughput DNA sequencing of the DNA barcodes, we aim to discern amplification properties and pinpoint the most promising saRNAs in terms of delivery efficiency and stability.
• Aim 2: In Vivo Exploration of Premier saRNAs in Distinct Cell Groups
  • Our uniquely crafted DNA barcoded saRNA library will serve as a potent tool to probe their attributes across diverse cells, tissues, and animal models, primarily using single-cell RNA sequencing (scRNA-seq).
  • The elite saRNAs identified in Aim 1 will be trialed in a preclinical murine model, allowing us to recognize the specific cell subsets that exhibit saRNA expression.
  • This entails administering either intranasal (IN) or intramuscular (IM) injections to skin explants or mice. Subsequently, tissues will be processed into a single-cell suspension and examined using avant-garde scRNA-seq technology.
• Aim 3: Experimental Trials of Forefront saRNAs in Preclinical Frameworks
  • Relying on the top saRNA constructs unearthed from Aims 1 and 2, we will gauge these designs over three separate saRNA platforms. This encompasses evaluations for an intranasal vaccine, a therapeutic vaccine, and a non-vaccine therapeutic modality.
  • This pivotal phase will unfold in synergy with the KRIBB research specialists.

The zenith of this research is projected to introduce state-of-the-art saRNA vectors and fundamental design doctrines. These revelations stand to catalyze transformative shifts in the therapeutic landscape by ensuring more streamlined and consistent protein delivery to targeted cell types. The therapeutic areas that are positioned to harvest the benefits from this research span genome editing modalities, oncology treatments, and advanced vaccination techniques.