A combinatorial library of triazine-cored polymeric vectors for pDNA delivery in vitro and in vivo

2017 ◽  
Vol 5 (21) ◽  
pp. 3907-3918 ◽  
Author(s):  
Mingxing Wang ◽  
Bo Wu ◽  
Jason D. Tucker ◽  
Peijuan Lu ◽  
Qilong Lu
Keyword(s):  
Combinatorial Library ◽  
Amphiphilic Polymers ◽  
Polymeric Vectors

Triazine-cored cationic amphiphilic polymers as potentially safe and effective carriers demonstrated in vitro and in vivo in mdx mice for pDNA delivery.

scholarly journals Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters

2018 ◽  
Vol 115 (26) ◽  
pp. E5859-E5866 ◽  
Author(s):  
Colin J. McKinlay ◽  
Nancy L. Benner ◽  
Ole A. Haabeth ◽  
Robert M. Waymouth ◽  
Paul A. Wender
Keyword(s):  
Small Molecules ◽  
Binary Mixtures ◽  
Combinatorial Library ◽  
Mrna Translation ◽  
Side Chain ◽  
Lipid Domains ◽  
Mrna Binding ◽  
Lipid Transporter

We report a strategy for generating a combinatorial library of oligonucleotide transporters with varied lipid domains and their use in the efficient transfection of lymphocytes with mRNA in vitro and in vivo. This library is based on amphiphilic charge-altering releasable transporters (CARTs) that contain a lipophilic block functionalized with various side-chain lipids and a polycationic α-amino ester mRNA-binding block that undergoes rearrangement to neutral small molecules, resulting in mRNA release. We show that certain binary mixtures of these lipid-varied CARTs provide up to a ninefold enhancement in mRNA translation in lymphocytes in vitro relative to either a single-lipid CART component alone or the commercial reagent Lipofectamine 2000, corresponding to a striking increase in percent transfection from 9–12% to 80%. Informed by the results with binary mixtures, we further show that CARTs consisting of optimized ratios of the two lead lipids incorporated into a single hybrid-lipid transporter molecule maintain the same delivery efficacy as the noncovalent mixture of two CARTs. The lead lipid CART mixtures and hybrid-lipid CARTs show enhanced lymphocyte transfection in primary T cells and in vivo in mice. This combinatorial approach for rapidly screening mRNA delivery vectors has provided lipid-varied CART mixtures and hybrid-lipid CARTs that exhibit significant improvement in mRNA delivery to lymphocytes, a finding of potentially broad value in research and clinical applications.

scholarly journals Triazine-cored polymeric vectors for antisense oligonucleotide delivery in vitro and in vivo

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Mingxing Wang ◽  
Bo Wu ◽  
Jason D. Tucker ◽  
Sapana N. Shah ◽  
Peijuan Lu ◽  
...  
Keyword(s):  
Antisense Oligonucleotide ◽  
Oligonucleotide Delivery ◽  
Polymeric Vectors

A Combinatorial Library of Indinavir Analogues and Its In Vitro and In Vivo Studies

2002 ◽  
Vol 12 (4) ◽  
pp. 529-532 ◽  
Author(s):  
Yuan Cheng ◽  
Thomas A Rano ◽  
Tracy T Huening ◽  
Fengqi Zhang ◽  
Zhijian Lu ◽  
...  
Keyword(s):  
Combinatorial Library ◽  
In Vivo Studies

scholarly journals The Hexapeptide Inhibitor of Galβ1,3GalNAc-specific α2,3-Sialyltransferase as a Generic Inhibitor of Sialyltransferases

2002 ◽  
Vol 277 (51) ◽  
pp. 49341-49351 ◽  
Author(s):  
Ki-Young Lee ◽  
Hyung Gu Kim ◽  
Mi Ran Hwang ◽  
Jung Il Chae ◽  
Jai Myung Yang ◽  
...  
Keyword(s):  
Trichoplusia Ni ◽  
Mammalian Cells ◽  
Combinatorial Library ◽  
Competitive Inhibitor ◽  
Strong Inhibition ◽  
Ovary Cells ◽  
Lectin Blot ◽  
Synthetic Hexapeptide

The mammalian Galβ1,3GalNAc-specific α2,3-sialyltransferase (ST3Gal I) was expressed as a secreted glycoprotein in High FiveTM(Trichoplusia ni) cells. Using this recombinant ST3Gal I, we screened the synthetic hexapeptide combinatorial library to explore a sialyltransferase inhibitor. We found that the hexapeptide, NH2-GNWWWW, exhibited the most strong inhibition of ST3Gal I among five different hexapeptides that were finally selected. The kinetic analysis of ST3Gal I inhibition demonstrated that this hexapeptide could act as a competitive inhibitor (Ki= 1.1 μm) on CMP-NeuAc binding to the enzyme. Moreover, the hexapeptide was shown to strongly inhibit bothN-glycan-specific α2,3- and α2,6-sialyltranferasein vitro, suggesting that this peptide may inhibit the broad range of sialyltransferases regardless of their linkage specificity. The inhibitory activityin vivowas investigated by RCA-I lectin blot analyses and by metabolicd-[6-3H]GlcNH2radiolabeling analyses ofN- andO-linked oligosaccharides in Chines hamster ovary cells. Our results demonstrate that the hexapeptide can act as a generic inhibitor of theN- andO-glycan-specific sialyltransferases in mammalian cells, which results in the significantly reduced NeuAc expression on cellular glycoproteinsin vivo.

Induction and Differentiation of Dental Epithelium in Vivo and in Vitro

1982 ◽  
Vol 40 ◽  
pp. 142-145
Author(s):  
E. J. Kollar
Keyword(s):  
Connective Tissue ◽  
Oral Mucosa ◽  
Basal Lamina ◽  
Functional Derivatives ◽  
Specific Source ◽  
Dental Epithelium ◽  
Connective Tissue Stroma

The differentiation and maintenance of many specialized epithelial structures are dependent on the underlying connective tissue stroma and on an intact basal lamina. These requirements are especially stringent in the development and maintenance of the skin and oral mucosa. The keratinization patterns of thin or thick cornified layers as well as the appearance of specialized functional derivatives such as hair and teeth can be correlated with the specific source of stroma which supports these differentiated expressions.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

Sign in / Sign up

Export Citation Format

Share Document