I would guess quite a bit, WPRE is used to stabilize long non terminated transcripts. It is used in lentivirus vectors to compensate for the fact that you cannot use polII termination sequences between the LTRs as this would terminate transcription during lenti production.

Given that lack of nuclear localization can have a profound impact on editing and gene perturbation efficiency, we suggest further investigation across both cultured and in-vivo postmitotic cell models.

Addition of a neuronal specific NLS (2X MeCP2) was able to rescue neuronal nuclear localization, expression level and improve activity when sgRNAs were delivered 2 weeks after differentiation

Other CRISPR enzymes we tested (nCas9 and Zim3) where also found mostly in the cytoplasm of neurons, but were not unstable in neurons

We found two neuronal specific issues: cytoplasmic mislocalization of CRISPR enzymes after differentiation and the destabilization of the KRAB domain outside the nucleus, which was specific to dCas9-KRAB (using the KOX1 domain).

This work was spearheaded by Gregory Cajka, brilliant graduate student in the lab, and Matthew Liu, extremely talented undergrad and post-bac research tech.