A research team has recently taken one more step toward enhancing the development of delivering drugs directly to target cells in nanoscale bubbles of fats, also known as lipid nanoparticles or LNPs.

As specified in a Phys.org report, therapeutics based on mRNA or messenger RNA can potentially cure an array of maladies, including genetic diseases, cancer, and, as the world has learned in previous years, fatal viruses.

For the drug delivery to work, they need to be delivered directly to target cells in nanoscale bubbles of fat; as earlier mentioned, mRNA is not good if it does not reach the right cell type.

Trainees in the lab of James Dahlman, Curtis Dobrowolski, and Kalina Paunovska have developed a system to develop preclinical nanoparticle studies more predictive.

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Nanoparticles
(Photo: Wikimedia Commons/National Institute of Standards and Technology )
On top of testing a drug's efficiency and how cell subtypes react to nanoparticles, researchers are identifying which genes are involved in the LNPs’ successful uptake.


DNA Barcoding

The Georgia Institute of Technology and Emory University's School of Medicine research team's discoveries published in the Nature Nanotechnology journal are already influencing the direction of research "in this growing competitive field."

According to Dahlman, associate professor and McCamish Foundation, Early Career Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory, he's very excited about this research and anticipating shifting most of their future projects to this approach.

To fast-track, the process of the efficacy of their LNPs, Dahlman and his team has developed an approach known as DNA barcoding.

In this method, the scientists insert a snippet of DNA corresponding to a given LNP. The LNPs are then injected, and cells are henceforth analyzed for the presence of the "barcodes"  with genetic sequencing.

The team determines which barcodes have reached particular targets, accentuating the most promising nanoparticles.

Since many DNA sequences can be read at once, the barcoding process enables many experiments to be carried out simultaneously, revving the discovery of effective lipid nanoparticle carriers.

Essentially, DNA barcoding has substantially enhanced the nanoparticle pre-clinical screening process, but there is still a substantial barrier affecting the delivery of drugs.

SENT-Seq

Due to their diversity, cells are kind of like moving targets. The team noted that cells previously thought to be homogeneous comprise distinct and varied cell subsets.

To test their hypothesis, the study authors developed a new tool to gauge all these things simultaneously. Essentially, their multi-omic nanoparticle delivery system is known as "single-cell nanoparticle targeting-sequencing or SENT-seq.

Using SENT-seq, the researchers were able to measure how LNPs deliver DNA barcodes and mRNA into cells, the subsequent protein production that the mRNA drug-facilitated, and the cell's identity,  in thousands of individual cells.

This multi-omics approach, in particular, could represent an essential leap forward for high-throughput LNP discovery. More so, the SENT-seq technique enabled them to determine cell subtypes that demonstrate specifically high or low nanoparticle uptake, not to mention the genes linked to those subtypes.

Therefore, on top of testing a drug's efficiency and how cell subtypes react to nanoparticles, they are identifying which genes are involved in the  LNPs' successful uptake, a similar Bioengineer.org report said.

Related information about mRNA_based therapies is shown on Creative Biolabs' YouTube video below:

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