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Review
. 2021 Apr 15:8:571076.
doi: 10.3389/fcvm.2021.571076. eCollection 2021.

Unresolved Issues in RNA Therapeutics in Vascular Diseases With a Focus on Aneurysm Disease

Isabel N Schellinger  1   2   3   4 , Angelika R Dannert  1 , Karin Mattern  1   2 , Uwe Raaz  1   2 , Philip S Tsao  5   6
Affiliations
Review

Unresolved Issues in RNA Therapeutics in Vascular Diseases With a Focus on Aneurysm Disease

Isabel N Schellinger et al. Front Cardiovasc Med. .

Abstract

New technologies have greatly shaped the scientific and medical landscape within the last years. The unprecedented expansion of data and information on RNA biology has led to the discovery of new RNA classes with unique functions and unexpected modifications. Today, the biggest challenge is to transfer the large number of findings in basic RNA biology into corresponding clinical RNA-based therapeutics. Lately, this research begins to yield positive outcomes. RNA drugs advance to the final phases of clinical trials or even receive FDA approval. Furthermore, the introduction of the RNA-guided gene-editing technology CRISPR and advances in the delivery of messenger RNAs have triggered a major progression in the field of RNA-therapeutics. Especially short interfering RNAs and antisense oligonucleotides are promising examples for novel categories of therapeutics. However, several issues need to be addressed including intracellular delivery, toxicity, and immune responses before utilizing RNAs in a clinical setting. In this review, we provide an overview on opportunities and challenges for clinical translation of RNA-based therapeutics, with an emphasis on advances in novel delivery technologies and abdominal aortic aneurysm disease where non-coding RNAs have been shown to play a crucial regulatory role.

Keywords: RNA; abdominal aortic aneurysm; cardiovascular medicine; epigenetics; innovation; non-coding RNAs; therapeutics.

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Conflict of interest statement

IS and UR are cofounders of Angiolutions. Angiolutions is a company developing vascular devices for aneurysm diseases. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overview over small RNA genesis and mode of action.
Figure 2
Figure 2
Overview over long non-coding RNA function and behavior.
Figure 3
Figure 3
Overview over different delivery system in the context of RNA therapeutics.
Figure 4
Figure 4
Overview showing off-target effects in the context of RNA therapeutics.
Figure 5
Figure 5
Non-coding RNAs that have been shown to play a major role in AAA disease.
See this image and copyright information in PMC

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