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Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
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Phase II Reactions: Methylation Reactions01:17

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Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
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Phase II Reactions: Acetylation Reactions01:24

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Acetylation, a phase II biotransformation reaction, introduces an acetyl group to drugs or their metabolites. Acetyltransferase enzymes facilitate this reaction, which resembles α-amino acid conjugation due to the addition of a functional group to the drug molecule.
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Nucleoside Triphosphates - From Synthesis to Biochemical Characterization
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Chemical Modifications in Nucleic Acid Therapeutics.

Kim A Lennox1, Rebecca C Young2, Mark A Behlke3

  • 1Integrated DNA Technologies, Inc., Coralville, IA, USA. klennox@idtdna.com.

Methods in Molecular Biology (Clifton, N.J.)
|August 28, 2025
PubMed
Summary
This summary is machine-generated.

Chemically modified nucleic acid-based therapies (NATs) are advancing rapidly, offering new treatments for rare diseases. Innovations in chemical modifications enhance drug efficacy and safety, paving the way for more nucleic acid medicines.

Keywords:
ASOAntisenseCRISPRCas12aCas9Chemical modificationGuide RNAOligonucleotidesRNAicrRNAmRNAsgRNAsiRNA

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Genetics

Background:

  • Nucleic acid-based therapies (NATs) are a growing drug class, driven by chemical modifications.
  • These therapies include gene expression inhibitors (ASOs, RNAi), gene structure modulators, mRNA therapeutics, and CRISPR/Cas gene editing tools.

Purpose of the Study:

  • To review chemical modifications used in NATs.
  • To highlight innovations improving efficacy and safety of nucleic acid drugs.
  • To discuss the future of nucleic acid medicine.

Main Methods:

  • Review of literature on chemical modifications in NATs.
  • Analysis of publications demonstrating milestones in oligonucleotide (ON) efficacy and safety.
  • Highlighting key innovations in chemical modifications.

Main Results:

  • Specific chemical modifications are crucial for the efficacy, safety, and cellular uptake of NATs.
  • Successful clinical applications and regulatory approvals demonstrate the potential of NATs.
  • Innovations are expanding the clinical capabilities of nucleic acid medicine.

Conclusions:

  • Chemical modifications are key to the success of NATs.
  • Further advancements in modifications will accelerate NATs into the clinic.
  • NATs hold promise for treating currently untreatable diseases.