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Human Virus-Like Proteins: Implications for Gene Therapy
Aya Al Othman1, Anna Polyanskaya1, Mikhail Durymanov1,2
1School of Biological and Medical Physics, Moscow Institute of Physics and Technology, Institutsky per. 9, Dolgoprudny, Moscow Region, 141701, Russia.
Current Gene Therapy
|May 27, 2024
Summary
Human proteins derived from transposons and viruses, like Peg10 and syncytins, have physiological roles. These virus-like proteins can be bioengineered into humanized particles for targeted mRNA delivery, offering potential gene therapy solutions.
Area of Science:
- Genomics
- Molecular Biology
- Biotechnology
Background:
- Mammalian genomes contain numerous DNA sequences of transposon or viral origin.
- Some endogenous retroviral elements and transposons encode functional proteins with physiological roles.
- Human proteins such as Peg10, Arc/Arg3.1, and syncytins share structural similarities with viral proteins (Gag, envelope).
Purpose of the Study:
- To review human proteins of viral or transposon origin and their biological functions.
- To highlight recent advances in bioengineering these proteins for targeted mRNA delivery.
- To discuss the prospects of these engineered particles in gene therapy and clinical applications.
Main Methods:
- Bioinformatic analysis of mammalian genomes to identify viral/transposon-derived sequences.
- Structural comparison of human virus-like proteins with retroviral proteins.
- Review of literature on the biological functions and bioengineering applications of these proteins.
Main Results:
- Identification of human proteins (Peg10, Arc/Arg3.1, syncytins) with structural homology to viral proteins.
- Demonstration of the potential to repurpose these proteins for bioengineering 'humanized' capsid particles.
- Highlighting the feasibility of using these particles for targeted mRNA delivery.
Conclusions:
- Human virus-like proteins offer a promising platform for developing efficient, non-viral vectors for gene therapy.
- Exploiting these endogenous elements can overcome the immunogenicity issues associated with traditional viral vectors.
- Further research into these proteins could advance targeted mRNA delivery and clinical gene therapy applications.
