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Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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Aptamer-Based Targeted Protein Degradation.

Yuan Liu1,2, Xu Qian1, Chunyan Ran1,2

  • 1Department of Pathology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.

ACS Nano
|March 21, 2023
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Summary

Targeted protein degradation (TPD) removes harmful proteins. Aptamer-based TPD offers precise protein targeting, showing promise for various diseases by overcoming current application challenges.

Keywords:
AptamersOligonucleotidesPROTACsTargeted protein degradation

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Protein homeostasis is vital for cellular function.
  • Misfolded or overexpressed proteins contribute to disease.
  • Targeted Protein Degradation (TPD) is a therapeutic strategy.

Purpose of the Study:

  • To review the progress of TPD technology.
  • To summarize challenges in TPD applications.
  • To highlight advances in aptamer-based TPD.

Main Methods:

  • Review of current literature on TPD.
  • Analysis of aptamer selection and application in TPD.
  • Discussion of challenges and future directions.

Main Results:

  • TPD utilizes small molecules or antibodies for protein recognition.
  • Aptamers offer high specificity and affinity for target proteins.
  • Aptamer-based TPD is an emerging area with significant potential.

Conclusions:

  • Aptamer-based TPD presents a novel approach for targeted protein removal.
  • Further research is needed to address current challenges and optimize applications.
  • This technology holds promise for treating various diseases.