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IRC-SET 2018 pp 335-347 | Cite as

Developing Modified Peptide Nucleic Acids to Regulate Dysregulated Splicing

  • Samuel Foo EnzeEmail author
  • Tristan Lim Yi Xuan
  • Jayden Kim Jun-Sheng
Conference paper

Abstract

Peptide Nucleic Acid (PNA) can stabilise the Tau Exon 10-Intron 10 self-regulatory RNA hairpin, known to regulate the alternative splicing of exon 10 in Microtubule-Associated Protein Tau (MAPT) transcript [1], and thus rescue the aberrant ratio of protein isoforms (4R/3R), preventing tauopathy. We used antisense PNA (ASPNA) and triplex-forming PNA (TFPNA) methods, and compared the effectiveness of both. We synthesised PNA oligomers using solid phase peptide synthesis (SPPS) and tested binding affinity to the RNA hairpin using polyacrylamide gel electrophoresis (PAGE). TFPNA is less costly and more efficient to synthesise, but has low binding affinity, whereas ASPNA costs more to synthesise but has a higher binding affinity.

Hypothesis—Binding a PNA strand to the Tau Exon 10-Intron 10 self-regulatory hairpin can rescue the aberrant ratio of 3R:4R isoforms and thus cure tauopathy.

Keywords

Antisense strands Alternative splicing Hairpins Hoogsteen base pair Missense mutation Peptide nucleic acid (PNA) Steric hindrance Isoform U1snRNP ASPNA TFPNA 

Notes

Acknowledgements

This project would not have been possible without the guidance and help of individuals who have extended their invaluable assistance in the completion of this project:

• Our external mentor, Mr. Alan Ong, for his immense help and advice throughout the course of our research

• Our internal teacher-mentor, Mrs. Elizabeth Foo, for guiding us through our internal school deadlines and keeping us up to date

• Assistant Professor Chen Gang, for regularly sending us informative emails related to our research topic as well as allowing us to use his lab for research

• NTU, RI and MOE-GEB for giving us this unique opportunity to participate in the programme

• Our friends and family who have morally supported us throughout our project.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Samuel Foo Enze
    • 1
    Email author
  • Tristan Lim Yi Xuan
    • 1
  • Jayden Kim Jun-Sheng
    • 1
  1. 1.Raffles InstitutionSingaporeSingapore

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