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Oligo Splicing and Chemical Modification

BOC Sciences has the expertise and capability to provide oligonucleotide modification services to clients worldwide. BOC Sciences' state-of-the-art facilities, advanced technology and experienced staff can provide you with a full range of splicing and chemical modifications to meet your biological, diagnostic and drug discovery needs.

What is Oligo Splicing and Chemical Modification?

Splicing refers to the editing of newly transcribed pre-messenger RNA (pre-mRNA) by removing introns (non-coding regions of the gene) and adding or joining exons (coding regions). Mature mRNA is thus created, which is then used as a template for the synthesis of specific proteins.

SSOs are short, synthetic, antisense, modified nucleic acids that base pair with pre-mRNA and disrupt the normal splicing repertoire of transcripts by blocking protein-RNA binding interactions between RNA-RNA base pairing or splicing units and pre-mRNA. SSOs support an effective and specific way to therapeutically target and alter splicing. Modifications in SSOs involve altering the phosphate backbone and/or sugar component of the oligonucleotide and adding chemical modifications aimed at altering splicing rather than causing degradation of the bound pre-mRNA.

Our Oligo Splicing and Chemical Modification Services Specification

ModificationDescriptionPrice
Phosphorodiamidate morpholino (PMO) oligo modificationPMO has a morpholine ring to replace the furanose ring in native nucleic acids and a neutral phosphodiester backbone to replace the negatively charged phosphodiester backbone. The neutral charge of PMO results in low binding to plasma proteins, which improves tolerance in vivo.Inquiry
2'-O-methyl-phosphorothioate (2'-OMePS) oligo modificationThe 2'-hydroxyl group of the 2'-OMePS ribose ring is replaced by a 2'-O-2-methoxyethyl and phosphate linkage. This modification makes it more stable in vivo, less susceptible to breakdown by nucleases, and still maintains its base-pairing function.Inquiry
LNA/ Amido-bridged nucleic acid (AmNA)/ Guanidine-bridged nucleic acid (GuNA) modificationLNA is a nucleotide analogue carrying an altered ribose in which a methylene bridge links the 2'-O to the 4'-C atom in the furanose ring. This bridge allows LNA to form a strict N-type conformation, thus promoting binding affinity to complementary RNAs. Both AmNA-modified SSO and GuNA-modified SSO exhibited higher exon skipping activity and efficient splicing regulation.Inquiry

Why Choose Oligo Splicing and Chemical Modification Service from BOC Sciences?

Frequently Asked Questions (FAQ)

What is splicing in oligonucleotide research?

Splicing is the process of editing pre-messenger RNA (pre-mRNA) by removing introns and joining exons, creating mature mRNA that serves as a template for protein synthesis. This is crucial for regulating gene expression and protein production.

How do splice-switching oligonucleotides (SSOs) work?

SSOs are modified antisense oligonucleotides that bind to pre-mRNA, disrupting normal splicing by blocking RNA-RNA interactions. This allows for the targeted modulation of gene expression, providing a tool for therapeutic applications.

What are the benefits of PMO modifications?

PMOs replace the sugar ring with a morpholine ring and use a neutral backbone, which reduces plasma protein binding. This modification improves tolerance and splicing efficiency in vivo.

How does 2'-OMePS modification improve stability?

2'-OMePS replaces the 2'-hydroxyl group with a 2'-O-2-methoxyethyl group, making the oligonucleotide more stable. It also protects against nuclease degradation while maintaining base-pairing functionality.

What is the advantage of LNA and AmNA modifications?

LNA and AmNA modifications enhance oligonucleotide binding to complementary RNA, improving splicing efficiency. These modifications are particularly useful in exon skipping and splicing regulation.

How does GuNA modification improve splicing activity?

GuNA-modified SSOs enhance exon skipping and improve splicing regulation by promoting efficient binding. This modification is ideal for controlling gene expression.

What purification methods are used for modified oligonucleotides?

We offer purification methods including desalting, PAGE, and HPLC to ensure high purity. These methods guarantee reliable and consistent results for your research.

References

  1. Roberts, T.C.; et al. Advances in oligonucleotide drug delivery. Nat Rev Drug Discov. 2020. 19(10): p. 673-694.
  2. Nan, Y; et al. Antisense Phosphorodiamidate Morpholino Oligomers as Novel Antiviral Compounds. Front Microbiol. 2018. 9: p. 750.
  3. Pires, V.B.; et al. Short (16-mer) locked nucleic acid splice-switching oligonucleotides restore dystrophin production in duchenne muscular dystrophy myotubes. PLoS One. 2017. 12(7): p. e0181065.
  4. Shimo, T.; et al. Design and in vitro evaluation of splice-switching oligonucleotides bearing locked nucleic acids, amido-bridged nucleic acids, and guanidine-bridged nucleic acids. Int J Mol Sci. 2021. 22(7).

Complementary Oligonucleotides Modifications Services

Oligonucleotides Modifications Knowledge Center

* Only for research. Not suitable for any diagnostic or therapeutic use.
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