Our insights from engineering genomes

Genome Biology’s recent special issue on Insights from Genome Editing highlights the valuable insights generated from engineering genomes using a collection of powerful genome editing tools.

The breaking news of the birth of twin Chinese babies whose CCR5 genes have been edited to give them protection from HIV, has once again put genome engineering at the center of heated discussion. Human and agricultural genome engineering have been the focus of many researchers, as well as policy making agencies, however, genome editing tools can be used not only in generating organisms with certain desired traits, but can also be used to learn more about particular biological mechanisms.

Genome editing in agriculture

Plant pathogen resistance has always been a desired trait for crops, which could solve the major problem of the high cost of agricultural production. Xiang Ji et al. look into the traditional CRISPR-Cas9 genome editing approach and find wide spread off-target effects could be a major obstacle to the application of this approach in agriculture. Therefore, they developed two new virus-inducible genome editing systems. They are able to show that the new systems could effectively reduce virus load with transient expression of Cas9 protein. The off-target sites seem rare in the transgenic plants before and after virus infection.

Even though CRISPR-Cas9 has allowed targeted genome editing of crops at base-pair precision, there are still obstacles that lie in the path to agricultural application. Armin Scheben and David Edwards discuss bottlenecks for genome edited crops from lab to farm, including the challenges in the discovery and prioritization of agronomic target genes and how strictly the governments choose to regulate the engineered crops. Christine Tait-Burkard and colleagues review recent progress in the application of genome editing to farmed animal species on issues that influence farm-animal productivity, health and welfare.

Towards precise editing

We would probably be more comfortable with genome engineered organisms if genome editing approaches could achieve zero off-target and no on-target errors. Ferhat Alkan and colleagues provide a new angle to assess CRISPR-Cas9 off-targeting effect; they focus on nucleic acid duplex energy parameters. Tao Guo and colleagues focus on the error pattern of non-homologous end joining induced by Cas9, and thereby design a paired guide RNA approach to harness accurate non-homologous end joining in genome editing.

Expanded tool box

Less controversial applications of genome editing tools such as for functional genomic research is no less challenging than genome editing in agriculture, requiring an expansion of alternative tools to suit various genomic regions. Yong Lei and colleagues review technological advances in the DNA methylation field, the remaining challenges facing current tools, and how future development of new tools could improve precise addition or removal of epigenetic marks.

The special issue also contains expanded base editing tools by Chao Li and colleagues to edit multiple copies of a herbicide resistant gene in plants; CRISPR-SKIP by Michael Gapinske and colleagues to program gene splicing with base editors; and the in vivo all-in-one adeno-associated virus delivery system for Neisseria meningtidis Cas9 by Raed Ibraheim and colleagues. The special issue also includes CRISPRO by Vivien A.C. Scheoonenberg and colleagues, which is a computational tool to gain mechanistic insights from CRISPR tiling screens, perform protein and nucleotide sequence-level annotations, as well as 3D visualization of protein structure to elucidate functional residues and predict phenotypic outcomes of genome editing.

With the expansion of genome editing tools and their applications, it is clear that measures to address our ethical concerns, including safety issues in human health and food need to step up. The insights of how precise genome editing could be achieved will be able to guide regulations over genome editing from different aspects. Our insights and future research will be important to push the field forward in a healthy direction.

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