A5050045575- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Lipid Membrane Structure and Behavior
- SARS-CoV-2 and COVID-19 Research
- Dendrimers and Hyperbranched Polymers
- Gold and Silver Nanoparticles Synthesis and Applications
- Diverse Music Education Insights
- Nanocluster Synthesis and Applications
- Animal Virus Infections Studies
- Quantum Dots Synthesis And Properties
The University of Texas Southwestern Medical Center
2020-2024
Polymers represent a promising therapeutic platform for extrahepatic messenger RNA (mRNA) delivery but are hampered by low in vivo efficacy due to polyplex serum instability and inadequate endosomal escape following systemic administration. Here, we report the rational design combinatorial synthesis of zwitterionic phospholipidated polymers (ZPPs) via cationic polymer postmodification alkylated dioxaphospholane oxides deliver mRNA spleen lymph nodes vivo. This modular approach readily...
Alteration of phospholipid chemistry in lipid nanoparticles (LNPs) can increase endosomal escape and control organ targeting.
Abstract Approximately 10% of Cystic Fibrosis (CF) patients, particularly those with CF transmembrane conductance regulator ( CFTR ) gene nonsense mutations, lack effective treatments. The potential correction therapy through delivery the CRISPR/Cas system to CF-relevant organs/cells is hindered by efficient genome editor carriers. Herein, we report improved Lung Selective Organ Targeting Lipid Nanoparticles (SORT LNPs) for Cas9 mRNA, sgRNA, and donor ssDNA templates, enabling precise...
Lipid nanoparticles (LNPs) represent the leading concept for mRNA delivery. Unsaturated lipids play important roles in nature with potential therapeutics, but are difficult to access through chemical synthesis. To systematically study role of unsaturation, modular reactions were utilized a library 91 amino lipids, enabled by synthesis unsaturated thiols. An ionizable lipid series (4A3) emerged from vitro and vivo screening, where 4A3 core citronellol-based (Cit) periphery as best. We studied...
Abstract Clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR‐associated (Cas) protein gene editing is poised to transform the treatment of genetic diseases. However, limited progress has been made toward precise DNA via homology‐directed repair (HDR) that requires careful orchestration complex steps. Herein, dendrimer‐based lipid nanoparticles (dLNPs) are engineered co‐encapsulate and deliver multiple components for in vivo HDR correction. BFP/GFP switchable HEK293 cells...
Within the field of lipid nanoparticles (LNPs) for RNA delivery, focus has been mainly placed on organ level which can mask cellular effects consequential to therapeutic applications. Here, we studied a pair LNPs with similar physical properties and discovered how chemistry ionizable amino control endogenous LNP identity, affecting uptake in liver altering outcomes model cancer. Although most accumulate after intravenous administration (suggesting that delivery is straightforward), observed...
Nanoparticle (NP) clusters with diameters ranging from 20 to 100 nm are reversibly assembled 5 gold (Au) primary particles coated glutathione (GSH) in aqueous solution as a function of pH the range 5.4 3.8. As is lowered, GSH surface ligands become partially zwitterionic and form interparticle hydrogen bonds that drive self-limited assembly metastable <1 min. Whereas up size stable against cluster–cluster aggregation for 1 day, 80 can be stabilized over this period via addition citrate equal...
Abstract Lipid nanoparticles (LNPs) represent the leading concept for mRNA delivery. Unsaturated lipids play important roles in nature with potential therapeutics, but are difficult to access through chemical synthesis. To systematically study role of unsaturation, modular reactions were utilized a library 91 amino lipids, enabled by synthesis unsaturated thiols. An ionizable lipid series (4A3) emerged from vitro and vivo screening, where 4A3 core citronellol‐based (Cit) periphery as best....
In this work, a series of linear-dendritic poly(ethylene glycol) (PEG) lipids (PEG-GnCm) were synthesized through strategy using sequential aza- and sulfa-Michael addition reactions. The effect modulating the hydrophobic domain PEG was systematically investigated for in vitro vivo small RNA delivery as surface-stabilizing component 5A2-SC8 dendrimer lipid-based nanoparticles (DLNPs). lipid alkyl lengths (C8, C12, C16) generations (G1, G2, G3) altered to create PEG-GnCm with different...
Messenger RNA (mRNA) has generated great attention due to its broad potential therapeutic applications, including vaccines, protein replacement therapy, and immunotherapy. Compared other nucleic acids (e.g., siRNA pDNA), there are more opportunities improve the delivery efficacy of mRNA through systematic optimization. In this report, we studied a high-throughput library 1200 functional polyesters for systemic delivery. We focused on chemical investigation hydrophobic optimization as method...