Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10.

Leber congenital amaurosis type 10 is a severe retinal dystrophy caused by mutations in the CEP290 gene. We developed EDIT-101, a candidate genome-editing therapeutic, to remove the aberrant splice donor created by the IVS26 mutation in the CEP290 gene and restore normal CEP290 expression. Key to this therapeutic, we identified a pair of Staphylococcus aureus Cas9 guide RNAs that were highly active and specific to the human CEP290 target sequence.

N4 virion DNA dependent-RNA polymerase: initiation sequences utilized by the enzyme on heterologous templates.

Bacteriophage N4 virion-encapsulated RNA polymerase, the enzyme responsible for transcription of the phage early RNAs, is unable to use duplex linear DNA as a template. In contrast to other RNA polymerases, the enzyme transcribes denatured N4 DNA with in vivo specificity. The promoter sequences for three sites of transcription initiation on the N4 genome have been determined and found to contain conserved sequences and two sets of inverted repeats.

The effect of neonatal treatment of male mice with antiandrogens and of females with androgens on the development of the os penis and os clitoridis.

The os penis in mice and rats is composed of a proximal intramembranous and endochondral osseous element and a distal cartilaginous, ossifying element. Female mice, but not rats, have a small os clitoridis which corresponds to the intramembranous part of the proximal element of the os penis. In mice of either sex a dense mesenchymatous formation ventral to the urethra is the anlage for the bones of the external genitalia.