Programmable epigenome editing by transient delivery of CRISPR epigenome editor ribonucleoproteins.

Programmable epigenome editors modify gene expression in mammalian cells by altering the local chromatin environment at target loci without inducing DNA breaks. However, the large size of CRISPR-based epigenome editors poses a challenge to their broad use in biomedical research and as future therapies. Here, we present Robust ENveloped Delivery of Epigenome-editor Ribonucleoproteins (RENDER) for transiently delivering programmable epigenetic repressors (CRISPRi, DNMT3A-3L-dCas9, CRISPRoff) and activator (TET1-dCas9) as ribonucleoprotein complexes into human cells to modulate gene expression.

Packaged delivery of CRISPR-Cas9 ribonucleoproteins accelerates genome editing.

Effective genome editing requires a sufficient dose of CRISPR-Cas9 ribonucleoproteins (RNPs) to enter the target cell while minimizing immune responses, off-target editing and cytotoxicity. Clinical use of Cas9 RNPs currently entails electroporation into cells , but no systematic comparison of this method to packaged RNP delivery has been made. Here we compared two delivery strategies, electroporation and enveloped delivery vehicles (EDVs), to investigate the Cas9 dosage requirements for genome editing.

Diagnosis of posttraumatic stress disorder with the MMPI: PK scale scores in somatization disorder.

Clinic patients with diagnoses of either major depression or somatization disorder were given the MMPI. Women with somatization disorder had high scores on Keane's MMPI scale (PK) for posttraumatic stress disorder. Following the procedure for the MMPI-2 (46 of the 49 PK items and MMPI-2 norms), 59% of the women with somatization disorder and 21% of the women with major depression would have T scores > or = 65 on the MMPI-2 scale although none of them were known to have developed psychiatric disorder after exposure to a life threatening event.

MMPI screening scales for somatization disorder.

44 items on the MMPI were identified which appear to correspond to some of the symptoms in nine of the 10 groups on the Perley-Guze checklist for somatization disorder (hysteria). This list was organized into two scales, one reflecting the total number of symptoms endorsed and the other the number of organ systems with at least one endorsed symptom. Full MMPIs were then obtained from 29 women with primary affective disorder and 37 women with somatization disorder as part of a follow-up study of a consecutive series of 500 psychiatric clinic patients seen at Washington University.