Abstract

The revolutionary technology of CRISPR/Cas systems and their extraordinary potential to address fundamental questions in every field of biological sciences has led to their developers being awarded the 2020 Nobel Prize for Chemistry. In agriculture, CRISPR/Cas systems have accelerated the development of new crop varieties with improved traits—without the need for transgenes. However, the future of this technology depends on a clear and truly global regulatory framework being developed for these crops. Some CRISPR-edited crops are already on the market, and yet countries and regions are still divided over their legal status. CRISPR editing does not require transgenes, making CRISPR crops more socially acceptable than genetically modified crops, but there is vigorous debate over how to regulate these crops and what precautionary measures are required before they appear on the market. This article reviews intended outcomes and risks arising from the site-directed nuclease CRISPR systems used to improve agricultural crop plant genomes. It examines how various CRISPR system components, and potential concerns associated with CRISPR/Cas, may trigger regulatory oversight of CRISPR-edited crops. The article highlights differences and similarities between GMOs and CRISPR-edited crops, and discusses social and ethical concerns. It outlines the regulatory framework for GMO crops, which many countries also apply to CRISPR-edited crops, and the global regulatory landscape for CRISPR-edited crops. The article concludes with future prospects for CRISPR-edited crops and their products.

Highlights

  • Agriculture is facing global challenges arising from the planet’s rapidly growing human population, expected to reach nine billion by 2050 [1]

  • Using Agrobacterium to deliver CRISPR reagents (Cas9 and guide RNA (gRNA) genes) typically leads to these genes being randomly integrated into the plant genome, and with the resulting plants being similar to transgenic plants [128]

  • CRISPR reagents for plant genome editing can take the form of DNA, RNA, or RNPs [127,132]

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Summary

Introduction

Agriculture is facing global challenges arising from the planet’s rapidly growing human population, expected to reach nine billion by 2050 [1]. Cas is characterized by the presence of higher eukaryote and prokaryote nucleotide-binding (HEPN) domains [79] It ranges in size from 900 to 1300 amino acids and requires a gRNA spacer of 22–30 nt to recognize target RNA sequences, followed by a protospacer flanking sequence (PFS). Starting by fusing CRISPR/dCas with an ADAR2 (a member of adenosine deaminase family acting on RNA) domain, scientists from MIT McGovern Institute for Brain Research developed new tools for creating temporary genome changes by editing RNA bases. These are referred to as RESCUE (RNA editing for specific C to U exchange) [84,85] and REPAIR (RNA editing for Programmable A to I (G) replacement) [84]. This section discusses examples of CRISPR/Cas system innovation in agriculture and biological sciences

Deactivated Cas Nuclease Systems Can Bind DNA but Not Cleave It
Classification of Genome Editing Modifications
SDN1 Systems
SDN2 Systems
SDN3 Systems
CRISPR Reagents
Plasmids
Messenger RNA
Delivery Methods in Plants
Direct Delivery Methods
Indirect Delivery Methods
Potential Concerns Associated with CRISPR Crops
Selection of Reagents for Creating Genome-Edited Crop Plants
Selection of Delivery Method
Off-Target Impacts
Gene Drives
Environmental Concerns
CRISPR-Edited Crops and GM Crops
Product-Based Regulation of GM Plants
Process-Based Regulation of GM Plants
Regulations for Plants with Novel Traits
Ethical Concerns and Public Acceptance of Genome-Edited and GM Crops
Global Regulation of GMOs and Genome-Edited Crops
United States
Canada
Latin America
European Union
Australia and New Zealand
Findings
10. Prospects
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