DNA/RNA Analysis / MALDI & Q-TOF

Applications for MALDI & Q-TOF

 
 

Synthesis Confirmation for Nucleic Acid Medicines - Rapid Sequence Confirmation Using a MALDI-TOF Mass Spectrometer

Medicines utilizing nucleic acids such as DNA and RNA that control genetic information are called "nucleic acid medicines". These nucleic acid medicines allow targeting of molecules such as messenger RNA (mRNA) and micro RNA (miRNA) which cannot be targeted with traditional low-molecular-weight drugs and antibody medicines, and are expected to be innovative  next generation pharmaceuticals for the treatment of genetic disorders which have been difficult to treat so far.

 
 
 
 
 
 

Oligonucleotide Mass Analysis and In-source Decay Sequencing on a MALDI TOF Mass Spectrometer

Mass spectrometry has the capacity to analyze oligonucleotides more quickly and accurately than many other techniques. These important factors become critical in a high throughput environment, for example in the case of industrial primer synthesis where tens of thousands of samples may be generated each day. Here, it is vital that the product quality is of a high standard and that the correct sequence has been generated. Limitations arise when the nature of the sample is considered. For example, electrospray experiments may be difficult due to the high salt content of synthesized primers that can suppress the ionization process, produce cationic salt adducts, and promote multiple charge states making spectral interpretation more complicated.

 
 
 
 
 
 

Determination of Molecular Mass and Quantification of Oligonucleotide Therapeutics Using Quadrupole Time-of-Flight Mass Spectrometer LCMS™-9030

Oligonucleotide therapeutics are synthetic oligonucleotides that demonstrate their medical efficacy through binding to target genes or target proteins that may be responsible for a range of diseases. To date, eight types of oligonucleotide therapeutics have been approved, many of which have a length of approximately 20 bases. As an oligonucleotide therapeutic, the 2’-MOE modified oligonucleotide having 20 bases was used.

 
 
 
 

Applications for MALDI & Q-TOF

Analysis of Oligonucleotide Therapeutics using MALDI-8030 and LCMS-9030

Molecular characterization of nucleic acids using mass spectrometry is of current growing interest, because oligonucleotide therapeutics are a promising medicine to cure some diseases by working at upper stream of action mechanism with fewer side effects. Whereas a high-resolution accurate ESI mass spectrometer enables an exact intact mass measurement, routine oligo sequence analysis is a still hurdle, using ESI instruments. The complete internal oligo sequence is rarely obtained using typical ESI-MS/MS technique. On the other hand, in-source decay (ISD) using MALDI-TOFMS was reported as a useful method to conduct sequence analysis, although the instruments often employed do not have sufficient specification for exact mass measurement. Here, we report the characterization of oligonucleotide therapeutics using ESI-QTOF, LCMS-9030, and a dual polarity benchtop linear MALDI-TOFMS, MALDI-8030.

 
 

Negative Mode Analysis of Synthetic Oligonucleotides using the MALDI-8030 Dual Polarity Benchtop MALDI-TOF Mass Spectrometer

Synthetic oligonucleotides are short DNA or RNA sequences which find different applications in molecular biology, such as primers used in DNA sequencing and amplification by the polymerase chain reaction (PCR). Recently, synthetic oligonucleotides have also been explored for therapeutic and diagnostic purposes, and DNA-based diagnostic test kits, in several conditions. Cystic fibrosis is an example of a condition which develops at the DNA level. It is the commonest autosomal recessive disorder among Caucasians and caused by mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is located on chromosomal region 7q31.2 and contains 27 exons.

 
 
 

Determination of Molecular Mass and Quantification of Oligonucleotide Therapeutics Using Quadrupole Time-of-Flight Mass Spectrometer LCMS™-9030

Oligonucleotide therapeutics are synthetic oligonucleotides that demonstrate their medical efficacy through binding to target genes or target proteins that may be responsible for a range of diseases. To date, eight types of oligonucleotide therapeutics have been approved, many of which have a length of approximately 20 bases. As an oligonucleotide therapeutic, the 2’-MOE modified oligonucleotide having 20 bases was used.

 
 
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