Journal
BIOLOGICAL REVIEWS
Volume 93, Issue 3, Pages 1649-1683Publisher
WILEY
DOI: 10.1111/brv.12413
Keywords
active DNA release; cellular breakdown mechanisms; circulating mitochondrial DNA; in vitro cell culture; lateral information transfer
Categories
Funding
- National Research Foundation (NRF), South Africa [SFH14061869958, SFH13092447078]
- George Forster Research Fellowship by the Alexander von Humboldt Foundation
- NRF
Ask authors/readers for more resources
Since the detection of cell-free DNA (cfDNA) in human plasma in 1948, it has been investigated as a non-invasive screening tool for many diseases, especially solid tumours and foetal genetic abnormalities. However, to date our lack of knowledge regarding the origin and purpose of cfDNA in a physiological environment has limited its use to more obvious diagnostics, neglecting, for example, its potential utility in the identification of predisposition to disease, earlier detection of cancers, and lifestyle-induced epigenetic changes. Moreover, the concept or mechanism of cfDNA could also have potential therapeutic uses such as in immuno- or gene therapy. This review presents an extensive compilation of the putative origins of cfDNA and then contrasts the contributions of cellular breakdown processes with active mechanisms for the release of cfDNA into the extracellular environment. The involvement of cfDNA derived from both cellular breakdown and active release in lateral information transfer is also discussed. We hope to encourage researchers to adopt a more holistic view of cfDNA research, taking into account all the biological pathways in which cfDNA is involved, and to give serious consideration to the integration of in vitro and in vivo research. We also wish to encourage researchers not to limit their focus to the apoptotic or necrotic fraction of cfDNA, but to investigate the intercellular messaging capabilities of the actively released fraction of cfDNA and to study the role of cfDNA in pathogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available