Abstract: The present disclosure provides methods of modifying the genome of a mammalian zygote. The present disclosure provides methods of modulating transcription in a mammalian zygote. The present disclosure provides methods of labeling a target nucleic acid in the genome of a mammalian zygote. The present disclosure provides methods of delivering a ribonucleoprotein complex into a mammalian zygote. The present disclosure provides methods of delivering a polypeptide or a nucleic acid into a mammalian zygote.

Abstract: An upper pen tube structure for pen is disclosed, wherein the spring is covered around an outer portion of the middle column, and two ends of the spring are pressed against an outwardly protruded rim of the middle column and a stopping portion of the tube respectively. Thereby, when a control button is pressed downward to reach a lower end of a chute in order to drive the middle column to move downward, the control button can be pushed inside a hook portion in order to fix the middle column's position, and when pushing the control button back inside the chute, the middle column can be pressed and pushed against by the spring in order to move upward along the chute of the tube to reach an upper end of the chute.

Abstract: A coupler sleeve for a pen and the pen using the coupler sleeve are provided, wherein the sleeve portion at the lower end of the main body is used for inserting into the upper opening of the lower pen tube to engage the outer protruded ring on the upper opening of the lower pen tube. Thereby, when a refill sleeve column for Cross-type refills is inserted inside the main body, a rotating portion of the refill sleeve column can be tightly sleeved in a fastening section of the sleeve portion, and the lower pen tube and the fastening section of the sleeve portion are pressed by the rotating portion in order to be fixed tightly and relatively at positions, so that the refill can be turned outside or inside of the lower pen tube by turning the upper pen tube and the lower pen tube relatively.