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Principal Investigator: Jayoung Kim
Organization: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
Fiscal Year: 2024
Award: $222,000
Funding agency: National Institute of Biomedical Imaging and Bioengineering
PROJECT SUMMARY / ABSTRACT
The proposed project aims to deliver a research tool that supports accurate and resource-
efficient biodistribution studies involving a library of gene-encapsulated nanoparticles. The
state-of-the-art technology to perform in vivo high-throughput screening of non-viral gene
delivery vectors is DNA/RNA barcoding, where oligonucleotides of unique sequence are used
as identifiable and quantifiable label for individual nanoparticles in a pooled mixture. However,
notwithstanding the exponentially growing number of novel gene-carrying nanoparticles,
researchers have not been equally attracted to in vivo high-throughput screening via this
barcoding technology. The long-term objective of our proposed study is to offer a broadly
accessible and therefore accepted tool for non-viral gene delivery research, by offering
several key innovative elements that address the shortcomings of the current method.
Specifically, our novel barcodes composed of deuterated peptoid, labelled Deuterated Oligo-
Peptoid Add-on as Nanoparticle Tracer (DOPANT), will demonstrate inert nanoparticle loading
process, biological stability, simplified extraction and purification protocols, as well as
affordable and sensitive detection method. To that end, the Emmitte group will synthesize
DOPANT barcodes, a library of 3-mer peptoids with varying molecular weights based on the
degree of deuteration and the choice of monomer, to be co-loaded with the genetic cargo into
nanoparticle formulations (Aim 1). The Kim group will then validate the DOPANT barcode-
labeled nanoparticles and their applications in a high-throughput biodistribution study. The
parameters in formulating a cocktail solution of multiple DOPANT-loaded nanoparticles will be
fine-tuned for optimal performance in biodistribution screening (Aim 2). Finally, DOPANT
barcode technology will be validated through a proof-of-principle, biodistribution study of 10
different mRNA-loaded lipid nanoparticles in healthy mice of two strains and both sexes (Aim
3). This collaborative project brings in the complementary expertise of two research groups to
develop a novel enabling tool that can advance and accelerate the path to clinical translation
for many existing and forthcoming nanoparticle designs.
Terms: <Acceleration><Address><Animals><Artificial nano particles><Artificial nanoparticles><Award><Bar Codes><Base Sequence><Behavior><Biodistribution><Biological><Biomedical Research><Body Tissues><Clinical><Communities><Consumption><DNA><DNA Therapy><Deoxyribonucleic Acid><Detection><Development><Disease><Disorder><Drug Kinetics><Elements><Encapsulated><Engineering><Ensure><Evaluation><Exhibits><Formulation><Gene Delivery><Gene Library><Gene Transfer Clinical><Genes><Genetic><Genetic Intervention><Genetic Materials><Goals><High Throughput Assay><Individual><Intervention><Intervention Strategies><Investigators><Label><Libraries><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Mediating><Messenger RNA><Methods><Mice><Mice Mammals><Molecular Weight><Murine><Mus><Non-Polyadenylated RNA><Non-Viral Vector><Nucleotide Sequence><Nucleotides><Oligo><Oligonucleotides><Organ><Peptoids><Performance><Pharmacokinetics><Process><Property><Protocol><Protocols documentation><R-Series Research Projects><R01 Mechanism><R01 Program><RNA><RNA Degradation><RNA Gene Products><Recovery><Reproducibility><Research><Research Grants><Research Personnel><Research Project Grants><Research Projects><Research Resources><Researchers><Resources><Ribonucleic Acid><Sampling><Screening procedure><Services><Side><Spinal Column><Spine><Standardization><Structure><Technology><Time><Tissues><Tracer><Vertebral column><backbone><barcode><biologic><clinical applicability><clinical application><clinical translation><clinically translatable><cost><deep sequencing><delivery vector><delivery vehicle><design><designing><detection method><detection procedure><detection technique><developmental><engineered nano particle><engineered nanoparticle><gene repair therapy><gene therapy><gene-based therapy><genetic library><genetic therapy><genomic therapy><high throughput screening><in vivo><innovate><innovation><innovative><interventional strategy><lipid based nanoparticle><lipid nanoparticle><mRNA><monomer><nano><nano label><nano particle><nano particle delivery><nano-sized particle><nanolabel><nanoparticle><nanoparticle delivered><nanoparticle delivery><nanosized particle><non-viral gene delivery><nonviral gene delivery><nonviral vector><novel><nucleic acid delivery><nucleic acid sequence><nucleic acid therapy><nucleic acid-based therapeutics><oligos><polypeptide><screening><screening tools><screenings><sex><side effect><site targeted delivery><support tools><targeted delivery><therapeutic nucleic acids><tool><transgene expression><vector>