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Hope, hype and harms of genome editing for heart disease

ESC Congress News 2019 - Paris, France

Genome editing is changing the landscape of cardiovascular research and also has the capacity to provide much-needed long-term solutions to cardiovascular diseases.1 But is it living up to the hype?

Basic Science

Prof. Serena ZacchignaProfessor Serena Zacchigna (University of Trieste and International Centre for Genetic Engineering and Biotechnology, Trieste, Italy), who co-chaired yesterday’s symposium ‘Genome editing for heart disease’, discusses the possibilities, challenges and limitations of this powerful tool.

“Genome editing involves altering the sequence of endogenous DNA using technologies that break and then repair the DNA, in order to either disrupt a DNA sequence or to replace an existing DNA sequence with a new one,” she explains. Editing is achieved with nucleases, the most recently introduced of which is CRISPR-Cas9. “The advantage of CRISPR-Cas9 over previous technologies, such as the TALENs (Transcription Activator-Like Effector Nucleases), is that it is cheaper and faster, and this has widened the opportunities to use genome editing technology,” says Prof. Zacchigna.

She describes the main ways that genome editing can be used in cardiovascular diseases. “In terms of treatment, in diseases with a genetic basis, genome editing will allow the correction of the causal mutation/s and, if used in utero, prevent the onset of some diseases.” The technique is also invaluable for creating in vivo and ex vivo disease models that mimic the human condition in order to improve understanding of it, help to develop effective treatments and move towards personalised medicine.

Prof. Zacchigna sees hopes and challenges for genomic editing. “The hope is to be able to expand the controlled use of this technology across countries worldwide. The challenge is doing this in a situation where different countries have different regulations, where there is no consensus on how best to regulate the technology, there are no agreements on its applications and the risks have yet to be properly defined and quantified.”

“International consensus is needed to address the challenges facing genome editing.”

Prof. Zacchigna wants to ensure that genome editing is made accessible to all countries, not just those with the most resources. “Because these technologies provide tremendous opportunities for research and treatment, collaboration and cooperation between countries is important to promote informed use. More-developed, better-funded countries can support developing countries by sharing the technology, promoting debate and defining the regulations.”

According to Prof. Zacchigna, many of the issues and concerns surrounding genome editing—including the use of viral vector delivery systems to modify gene function and whether to restrict its use to somatic cells or to also allow manipulation of germ cells—have already been discussed in the context of gene therapy. “Of course,” she says, “there are also some other perspectives to consider, such as gene drive technology, used for example in pest control, which increases the probability that an artificially modified gene will be passed on to offspring. This highlights the need to identify the risks, find ways to limit them and also ensure that we have systems in place to control the technology.”

Currently, one of the main limitations to genome editing is reliable targeting. “It is currently difficult to predict where other mutations, away from the desired locus, might occur and it is expensive to track them using whole genome sequencing. Higher specificity CRISPR-Cas9 variants are required and a number of hi-fidelity variants are already emerging.” Other limitations include low efficiency, particularly in post-mitotic tissues, and anti-Cas9 immune responses.

Prof. Zacchigna is confident of the promise of genome editing, but is realistic when it comes to its emergence as a standard clinical tool in cardiovascular medicine. “Its first applications in the clinic are likely to be in diseases for which ex vivo genome editing are appropriate. A typical example is the case of blood cells that can be harvested from a patient, edited to delete genes that hamper the immune response to cancer (PD-1) or act as co-receptors for HIV-1 infection (CCR5), and then re-infused into the same patient. For direct in vivo editing—particularly for tissues that don’t undergo spontaneous regeneration and renewal, such as those of the cardiovascular system—genome editing is probably at least 10 years away.”



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1. Musunuru K. J Am Coll Cardiol 2017;70:2808–2821.

Notes to editor

About the European Society of Cardiology

The European Society of Cardiology brings together healthcare professionals from more than 150 countries, working to advance cardiovascular medicine and help people lead longer, healthier lives.

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ESC Congress is the world’s largest and most influential cardiovascular event contributing to global awareness of the latest clinical trials and breakthrough discoveries. ESC Congress 2019 takes place 31 August to 4 September at the Paris Expo Porte de Versailles, Paris - France. Explore the scientific programme