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Related Experiment Videos

RASONs: a novel antisense oligonucleotide therapeutic approach for asthma.

A Sandrasagra1, L Tang, S A Leonard

  • 1Epigenesis Pharmaceuticals, Inc., Cranbury, New Jersey 08512, USA. asandrasagra@EpiGene.com

Expert Opinion on Biological Therapy
|December 1, 2001
PubMed
Summary

Inhaled antisense oligonucleotides (ASONS) offer targeted delivery to the lungs for respiratory diseases. EPI-2010, a respirable ASON, effectively improved asthma models by inhibiting adenosine A(1) receptor expression.

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Area of Science:

  • Pharmacology
  • Respiratory Medicine
  • Oligonucleotide Therapeutics

Background:

  • Antisense oligonucleotides (ASONS) can modulate gene expression.
  • Local delivery to the respiratory tract is challenging for systemic drugs.
  • Asthma involves discordantly expressed genes, including the adenosine A(1) receptor.

Purpose of the Study:

  • To evaluate EPI-2010, a respirable ASON, for targeted delivery to the lungs.
  • To assess the efficacy of EPI-2010 in inhibiting adenosine A(1) receptor expression and improving asthma.
  • To determine the safety and pharmacokinetic profile of inhaled EPI-2010.

Main Methods:

  • EPI-2010, a respirable ASON targeting the adenosine A(1) receptor, was administered via aerosol inhalation.
  • Efficacy was assessed in animal models of allergen-induced asthma, measuring airway obstruction and hyper-responsiveness.

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  • Absorption, distribution, metabolism, excretion (ADME), and safety studies were conducted.

    • Main Results:

    • Inhaled EPI-2010 successfully delivered ASONs to the lung.
    • EPI-2010 significantly inhibited adenosine A(1) receptor expression.
    • Treatment with EPI-2010 markedly improved asthma symptoms in animal models.
    • Safety and ADME studies indicated low, safe, and long-acting doses were achievable.

    Conclusions:

    • Respirable ASONs like EPI-2010 provide a viable strategy for targeted respiratory disease treatment.
    • This approach allows for safe and effective local delivery, avoiding systemic side effects.
    • The RASON technology facilitates accelerated in vivo target validation and therapeutic discovery for respiratory conditions.