July 5, 2022 -- Researchers in Georgia have developed a system to make preclinical nanoparticle studies more predictive that combines DNA barcoding with a multiomic nanoparticle delivery system called single-cell nanoparticle targeting-sequencing (SENT-seq).
Curtis Dobrowolski and Kalina Paunovska, trainees in the lab of James Dahlman at the Georgia Institute of Technology and Emory University's School of Medicine inserted a snippet of DNA that corresponds to a given lipid nanoparticle (LNP) that is then injected into a cell, which is subsequently examined for the presence of the "barcodes" using genetic sequencing.
The system identifies which barcodes have reached which specific targets and because many DNA sequences can be read at once, the barcoding process allows several experiments to be performed simultaneously, which accelerates the discovery of effective lipid nanoparticle carriers.
Already, DNA barcoding has significantly improved the nanoparticle preclinical screening process at the researchers' institutions and yet also they recognize that the chemical and genetic heterogeneity of cells influences how well LNPs can deliver mRNA therapies into the cells.
Using SENT-seq, the researchers quantified how LNPs delivered DNA barcodes and mRNA into cells, the subsequent protein production facilitated by the mRNA drug, and the identity of the cell. The approach allowed the team to identify cell subtypes that demonstrate high or low nanoparticle uptake, and the genes associated with those subtypes.
That means in addition to testing the efficacy of a drug and how certain cell subtypes react to nanoparticles, the researchers determined which genes were involved in the successful uptake of LNPs.
The research was supported by the National Institutes of Health.