Combination Therapy Using Inhalable GapmeR and Recombinant ACE2 for COVID-19

Area of Science:

• Biotechnology
• Antiviral Therapies
• Molecular Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19.
• Current treatments have limitations in effectively eradicating the virus.
• Antisense technology offers a targeted approach to inhibit viral replication.

Purpose of the Study:

• To propose a novel therapeutic strategy for COVID-19 by combining GapmeR technology with recombinant ACE2.
• To explore the potential of GapmeR technology for targeting intracellular SARS-CoV-2 RNA.
• To investigate the role of recombinant ACE2 in neutralizing extracellular SARS-CoV-2.

Main Methods:

• GapmeR, a cell-permeating antisense DNA, designed to target intracellular SARS-CoV-2 RNA.
• RNase H-mediated degradation of the viral RNA/DNA hybrid formed by GapmeR.
• Recombinant ACE2 protein to bind and neutralize extracellular SARS-CoV-2 spike glycoprotein.
• Delivery via inhalation or nebulization for patients and as prophylaxis for healthcare workers.

Main Results:

• GapmeR's mechanism involves binding to viral RNA, leading to its degradation within host cells.
• Recombinant ACE2 acts extracellularly, potentially blocking viral entry by binding to the S glycoprotein.
• The combination therapy aims for synergistic antiviral effects against SARS-CoV-2.

Conclusions:

• Combining SARS-CoV-2-targeted GapmeRs with recombinant ACE2 presents a promising therapeutic strategy.
• This approach offers a rapidly implementable and potentially highly effective method for COVID-19 treatment.
• The proposed therapy could significantly contribute to eradicating SARS-CoV-2 and saving lives.