Many bacterial and archaeal organisms use clustered regularly interspaced short palindromic repeats–CRISPR associated (CRISPR–Cas) systems to defend themselves from mobile genetic elements. These CRISPR–Cas systems are classified into six types based on their composition and mechanism. CRISPR–Cas enzymes are widely used for genome editing and offer immense therapeutic opportunity to treat genetic diseases. To realize their full potential, it is important to control the timing, duration, efficiency and specificity of CRISPR–Cas enzyme activities. In this Review we discuss the mechanisms of natural CRISPR–Cas regulatory biomolecules and engineering strategies that enhance or inhibit CRISPR–Cas immunity by altering enzyme function. We also discuss the potential applications of these CRISPR regulators and highlight unanswered questions about their evolution and purpose in nature.

许多细菌和古细菌生物使用聚集的规则间隔的短回文重复-CRISPR相关（CRISPR-Cas）系统来保护自己免受移动遗传元件的侵害。这些 CRISPR-Cas 系统根据其组成和机制分为六种类型。CRISPR–Cas 酶广泛用于基因组编辑，并为治疗遗传疾病提供了巨大的治疗机会。为了充分发挥其潜力，控制 CRISPR-Cas 酶活性的时间、持续时间、效率和特异性非常重要。在这篇综述中，我们讨论了天然 CRISPR-Cas 调控生物分子的机制以及通过改变酶功能来增强或抑制 CRISPR-Cas 免疫的工程策略。