Table Info

Table 4.

Advantages and limitations of different protein knockdown approaches

Method	Advantages and limitations
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	Advantages: More specific Can target splice variants or mutant forms For both membranous and intracellular proteins Limitations: Time-consuming Off-target effects Immunogenicity Needs modifications for netter delivery and stability
TRIM-Away	Advantages: 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

Method

Advantages and limitations

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

Advantages:

More specific
Can target splice variants or mutant forms
For both membranous and intracellular proteins

Limitations:

Time-consuming
Off-target effects
Immunogenicity
Needs modifications for netter delivery and stability

TRIM-Away

Advantages:

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

Declarations

Acknowledgments

The authors acknowledge institutional infrastructure support useful for this work.

Author contributions

AD: Conceptualization, Supervision, Writing—original draft, Writing—review & editing. MJ: Formal analysis, Writing—original draft, Writing—review & editing. PD: Writing—original draft, Writing—review & editing.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

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