Re-Entrant Polymorphism in Binary Mixtures Containing a Side Chain Polysiloxane

Author(s):  
M. Schlossarek ◽  
M. Naumann ◽  
A. Mädicke ◽  
B. Krücke ◽  
F. Kuschel ◽  
...  
Keyword(s):  
2018 ◽  
Vol 115 (26) ◽  
pp. E5859-E5866 ◽  
Author(s):  
Colin J. McKinlay ◽  
Nancy L. Benner ◽  
Ole A. Haabeth ◽  
Robert M. Waymouth ◽  
Paul A. Wender

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.


1980 ◽  
Vol 77 ◽  
pp. 445-449 ◽  
Author(s):  
Zohra Ferhat-Hamida ◽  
Robert Philippe ◽  
Jean-Claude Merlin ◽  
V. Kehiaian

1998 ◽  
Vol 95 (6) ◽  
pp. 1351-1354 ◽  
Author(s):  
C.-M. Bouché ◽  
P. Le Barny ◽  
H. Facoetti ◽  
F. Soyer ◽  
P. Robin
Keyword(s):  

1984 ◽  
Vol 51 (03) ◽  
pp. 358-361 ◽  
Author(s):  
H Bechtold ◽  
K Andrassy ◽  
E Jähnchen ◽  
J Koderisch ◽  
H Koderisch ◽  
...  

SummaryIn 8 patients on no oral intake and with parenteral alimentation, administration of cephalosporins with N-methyl-thiotetrazole side chain (moxalactam, cefamandole), was associated with prolongation of prothrombin time, appearance in the circulation of descarboxy-prothrombin (counter immunoelectrophoresis and echis carinatus assay) and diminution of protein C. Acute administration of 10 mg vitamin Ki was followed by the transient appearance of vitamin K1 2,3-epoxide, indicating an impaired hepatocellular regeneration of vitamin K1 from the epoxide. Impaired hepatic vitamin K1 metabolism, tentatively ascribed to the N-methyl-thiotetrazole group, is one (but possibly not the only) cause of bleeding complications and depression of vitamin K1dependent procoagulants in patients treated with the new class of cephalosporins.


Sign in / Sign up

Export Citation Format

Share Document