scholarly journals Automated Fast-Flow Synthesis of Antisense Phosphorodiamidate Morpholino Oligomers

Author(s):  
Chengxi Li ◽  
Alexander J. Callahan ◽  
Mark D. Simon ◽  
Kyle A. Totaro ◽  
Alexander J. Mijalis ◽  
...  

<p>The antisense phosphorodiamidate morpholino oligomer (PMO) drugs Eteplirsen and Golodirsen are improving the lives of some Duchenne muscular dystrophy (DMD) patients, but treating all DMD subtypes would require the development of over 50 novel antisense therapies. To rapidly prototype personalized PMO for diseases such as DMD, we designed a fully automated flow-based oligonucleotide synthesizer. Our optimized high temperature synthesis platform reduces coupling times by up to 22-fold compared to previously reported batch methods. We demonstrate the power of our new automated technology with the synthesis of milligram quantities of an 18-mer reporter PMO sequence in 3.5 hours, three new potential therapeutic PMO sequences targeted to exon 46 of the dystrophin gene in a single day, and a candidate antiviral PMO sequence targeted to the SARS-CoV-2 genomic mRNA in 3.5 hours. This flexible flow synthesis platform can be used for on-demand production of a broad range of personalized therapeutic polymers.</p>

2020 ◽  
Author(s):  
Chengxi Li ◽  
Alexander J. Callahan ◽  
Mark D. Simon ◽  
Kyle A. Totaro ◽  
Alexander J. Mijalis ◽  
...  

<p>The antisense phosphorodiamidate morpholino oligomer (PMO) drugs Eteplirsen and Golodirsen are improving the lives of some Duchenne muscular dystrophy (DMD) patients, but treating all DMD subtypes would require the development of over 50 novel antisense therapies. To rapidly prototype personalized PMO for diseases such as DMD, we designed a fully automated flow-based oligonucleotide synthesizer. Our optimized high temperature synthesis platform reduces coupling times by up to 22-fold compared to previously reported batch methods. We demonstrate the power of our new automated technology with the synthesis of milligram quantities of an 18-mer reporter PMO sequence in 3.5 hours, three new potential therapeutic PMO sequences targeted to exon 46 of the dystrophin gene in a single day, and a candidate antiviral PMO sequence targeted to the SARS-CoV-2 genomic mRNA in 3.5 hours. This flexible flow synthesis platform can be used for on-demand production of a broad range of personalized therapeutic polymers.</p>


2007 ◽  
Vol 43 (4) ◽  
pp. 239-242
Author(s):  
S. Kh. Suleimanov ◽  
O. A. Dudko ◽  
V. G. Dyskin ◽  
Z. S. Settarova ◽  
M. U. Dzhanklych

2015 ◽  
Vol 25 (12) ◽  
pp. 659-665
Author(s):  
Sin Hyong Joo ◽  
Hayk H. Nersisyan ◽  
Tae Hyuk Lee ◽  
Young Hee Cho ◽  
Hong Moule Kim ◽  
...  

2021 ◽  
Vol 11 (5) ◽  
pp. 2426
Author(s):  
Vladimir Promakhov ◽  
Alexey Matveev ◽  
Nikita Schulz ◽  
Mikhail Grigoriev ◽  
Andrey Olisov ◽  
...  

Currently, metal–matrix composite materials are some of the most promising types of materials, and they combine the advantages of a metal matrix and reinforcing particles/fibres. Within the framework of this article, the high-temperature synthesis of metal–matrix composite materials based on the (Ni-Ti)-TiB2 system was studied. The selected approaches make it possible to obtain composite materials of various compositions without contamination and with a high degree of energy efficiency during production processes. Combustion processes in the samples of a 63.5 wt.% NiB + 36.5 wt.% Ti mixture and the phase composition and structure of the synthesis products were researched. It has been established that the synthesis process in the samples proceeds via the spin combustion mechanism. It has been shown that self-propagating high-temperature synthesis (SHS) powder particles have a composite structure and consist of a Ni-Ti matrix and TiB2 reinforcement inclusions that are uniformly distributed inside it. The inclusion size lies in the range between 0.1 and 4 µm, and the average particle size is 0.57 µm. The obtained metal-matrix composite materials can be used in additive manufacturing technologies as ligatures for heat-resistant alloys, as well as for the synthesis of composites using traditional methods of powder metallurgy.


Author(s):  
Xiaoqiao Li ◽  
Linming Zhou ◽  
Han Wang ◽  
Dechao Meng ◽  
Guannan Qian ◽  
...  

Crystalline materials are routinely produced via high-temperature synthesis and show size-dependent properties; however, a rational approach to regulating their crystal growth has not been established. Here we show that dopants...


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