Advantages and limitations of different protein silencing techniques

TechnologyTargetAdvantagesDisadvantages
RNAi

RNA

  • Can be used for either short-term or long-term silencing effect

  • Supports both synthetic or genetic delivery methods to target cell

  • Cost-effective and easy to use

  • Can be used for inducible genetic knockdown

  • High off-target effect

  • Mostly provide partial knockdown of target

  • Activation of compensatory pathway

  • Not effective for proteins with long half-life

CRISPR-Cas9

DNA

  • Gene editing with a complete knockout of a gene or a gene segment

  • Precision

  • Irreversible process

  • High feasibility

  • Time-consuming

  • Essential gene knockouts are lethal

  • Difficult to aim larger proteins

  • Off-target effect generating indels

Targeted protein knockdown

Protein

  • Directly eliminates target protein

  • Can target essential or undruggable proteins

  • Rapid, hence low chances of compensatory activation

  • Less chance of immune response

  • Tedious design and synthesis challenge

  • Expensive