Advantages and limitations of different protein knockdown approaches
PROTAC
Advantages:
Can be used for undruggable molecules
Targeted degradation
Low toxicity
Avoids development of drug resistance
Limitations:
Requires prior chemical synthesis
Off-target activity
Only for intracellular protein
Intrabodies
More specific
Can target splice variants or mutant forms
For both membranous and intracellular proteins
Time-consuming
Off-target effects
Immunogenicity
Needs modifications for netter delivery and stability
TRIM-Away
High specificity
Rapid and easy to use
Does not require prior chemical synthesis
Can target specific PTMs
Limitations
Require highly-specific antibodies
Lack of in vivo validation
Requires exogenous delivery of antibody