Guide Therapeutics, Inc. has patented technologies to test thousands of chemically distinct nanoparticles in vivo. This enables us to identify simple, scalable, and clinically relevant nanoparticles that target new cell types efficiently and safely.
This technology utilizes DNA barcodes, which are DNA sequences that are rationally designed to act as molecular tags for specific nanoparticles. Tagging individual nanoparticles with barcodes and injecting many in parallel industrializes nanoparticle discovery, allowing Guide to perform thousands of nanoparticle experiments simultaneously.
Tracking Nanoparticles with DNA Barcodes
A nanoparticle is made to carry both a DNA barcode and a nucleic acid drug that reports whether the payload has been functionally delivered into the cytoplasm or nucleus. The cell only becomes reporter positive if the drug works inside the cell.
After administration in vivo, reporter positive cells are isolated and nanoparticles that delivered barcodes in those cells are identified via deep sequencing. By analyzing how hundreds of nanoparticles deliver drugs to any combination of desired on- and off-target cells, nanoparticles with high selectivity to target cells and low off-target effects are identified. This approach enables Guide Therapeutics to generate in vivo drug delivery data at a rate up to 15,000-fold higher than a traditional experiment. By performing these analyses iteratively, Guide can rapidly improve nanoparticle delivery.
The Dahlman Lab has shown the value of in vivo screening by demonstrating that in vitro nanoparticle screens (which are used throughout the field) do not predict in vivo delivery.