|Cancer model quality||
Transplantation models: limited by lack of immune system.|
Autochthonous models: high quality.
|High-quality given autochthonous nature.|
|Tissue delivery of components||
Can be technically challenging. Options include:|
- Transfection, with or without PB/SB: allows multiplexing; limited to certain organs.
- Lentivirus or AAV: wide range of tissues are accessible; relatively limited cargo capacity.
- Nanoparticles: high cargo capacity, low immunogenicity.
|Constitutive and conditional transposase mouse knock-in alleles are available. No further delivery of exogenous components is required.|
|Efficiency of mutations||
High efficiency in vitro (for transplantation model).|
In vivo mutagenesis has typically lower efficiency than in vitro.
|High efficiency of gene disruption in vivo; gene activation efficiency is variable. Therefore, TSGs are more identifiable than oncogenes1.|
|Types of mutations||
Disruption or activation of expression.|
Drop-out screens are not possible.
|Alleles targeted||Can induce mutations in both alleles of diploid cells||Usually only one allele is mutated in diploid cells.|
|Unwanted genetic effects||
Low off-target effects.|
On-target unintended effects may occur.
Footprint mutations with SB.
|Genome coverage in screen||
Focused or genome-wide libraries.|
High library coverage can be challenging to achieve in vivo.
Whole-genome including non-coding regions.|
PB favors open chromatin.
SB and PB have differing integration preferences.
|Time to conduct screen||Relatively short: direct injection of CRISPR components into tissues is required.||Relatively long: compound mutant mice (typically three or four alleles) need generating.|
|Costs of screen||Relatively low.||High costs due to long mouse breeding times.|