Assaying for peptides in individual
            <i>Aplysia</i>
            neurons with mass spectrometry

Chiu, Daniel T.; Zare, Richard N.

doi:10.1073/pnas.95.7.3338

Cited by 13 publications

(2 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The variables and their initial values used in the above equations are described in Table 1 . The model contains nine parameters obtained from direct experimental measurements and published literature, 18 , 22 , 23 , 24 , 25 as illustrated in Table 1 . We modeled these differential equations in the Simbiology toolbox developed for MATLAB users (code is included in the Supplemental Information ; The Mathworks).…”

Section: Resultsmentioning

confidence: 99%

Mathematical Modeling: A Tool for Optimization of Lipid Nanoparticle-Mediated Delivery of siRNA

Mihaila¹,

Ruhela²,

Keough

et al. 2017

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

Lipid nanoparticles (LNPs) have been used to successfully deliver small interfering RNAs (siRNAs) to target cells in both preclinical and clinical studies and currently are the leading systems for in vivo delivery. Here, we propose the use of an ordinary differential equation (ODE)-based model as a tool for optimizing LNP-mediated delivery of siRNAs. As a first step, we have used a combination of experimental and computational approaches to develop and validate a mathematical model that captures the critical features for efficient siRNA-LNP delivery in vitro. This model accurately predicts mRNA knockdown resulting from novel combinations of siRNAs and LNPs in vitro. As demonstrated, this model can be effectively used as a screening tool to select the most efficacious LNPs, which can then further be evaluated in vivo. The model serves as a starting point for the future development of next generation models capable of capturing the additional complexity of in vivo delivery.

show abstract

Section: Resultsmentioning

confidence: 99%

Mathematical Modeling: A Tool for Optimization of Lipid Nanoparticle-Mediated Delivery of siRNA

Mihaila¹,

Ruhela²,

Keough

et al. 2017

Molecular Therapy - Nucleic Acids

View full text Add to dashboard Cite

show abstract

“…If this hypothesis is correct, by using the ICP–MS nanoshell uptake result for NS-PLL-ssDNA (∼141 nanoshells/cell) and the number of ssDNA released extracellularly below 37 °C (∼1000 ssDNA/NS), then a maximum of ∼141 000 antisense oligonucleotides would be released inside the cell. After converting this number to moles and dividing by the intracellular volume (4 × 10 –12 L), , we can estimate that ∼60 nM of antisense oligonucleotides are delivered inside each cell via light-triggered release from the NS-PLL vector. This approximate concentration correlates well to the ∼50% GFP downregulation we observed, according to both previously reported experimental results and theoretical models. ,, Although this is an approximation, it points to future capabilities for delivering known amounts of therapeutic molecules using vectors such as our poly- l -lysine nanoshell complex at specific time points, to study the kinetics of physical, chemical, and biological processes within live cells.…”

Section: Resultsmentioning

confidence: 99%

Gene Silencing by Gold Nanoshell-Mediated Delivery and Laser-Triggered Release of Antisense Oligonucleotide and siRNA

et al. 2012

View full text Add to dashboard Cite

The approach of RNA interference (RNAi)- using antisense DNA or RNA oligonucleotides to silence activity of a specific pathogenic gene transcript and reduce expression of the encoded protein- is very useful in dissecting genetic function and holds significant promise as a molecular therapeutic. A major obstacle in achieving gene silencing with RNAi technology is the systemic delivery of therapeutic oligonucleotides. Here we demonstrate an engineered gold nanoshell (NS)-based therapeutic oligonucleotide delivery vehicle, designed to release its cargo on demand upon illumination with a near-infrared (NIR) laser. A poly(L)lysine peptide (PLL) epilayer covalently attached to the NS surface (NS-PLL) is used to capture intact, single-stranded antisense DNA oligonucleotides, or alternatively, double-stranded short-interfering RNA (siRNA) molecules. Controlled release of the captured therapeutic oligonucleotides in each case is accomplished by continuous wave NIR laser irradiation at 800 nm, near the resonance wavelength of the nanoshell. Fluorescently tagged oligonucleotides were used to monitor the time-dependent release process and light-triggered endosomal release. A green fluorescent protein (GFP)-expressing human lung cancer H1299 cell line was used to determine cellular uptake and gene silencing mediated by the NS-PLL carrying GFP gene-specific single-stranded DNA antisense oligonucleotide (AON-GFP), or a double-stranded siRNA (siRNA-GFP), in vitro. Light-triggered delivery resulted in ∼ 47% and ∼49% downregulation of the targeted GFP expression by AON-GFP and siRNA-GFP, respectively. Cytotoxicity induced by both the NS-PLL delivery vector and by laser irradiation is minimal, as demonstrated by a XTT cell proliferation assay.

show abstract

Sample Preparation for Hyphenated Analytical Techniques

Rosenfeld¹

2004

View full text Add to dashboard Cite

Assaying for peptides in individual Aplysia neurons with mass spectrometry

Cited by 13 publications

References 31 publications

Mathematical Modeling: A Tool for Optimization of Lipid Nanoparticle-Mediated Delivery of siRNA

Mathematical Modeling: A Tool for Optimization of Lipid Nanoparticle-Mediated Delivery of siRNA

Gene Silencing by Gold Nanoshell-Mediated Delivery and Laser-Triggered Release of Antisense Oligonucleotide and siRNA

Sample Preparation for Hyphenated Analytical Techniques

Contact Info

Product

Resources

About