If you have access to a Ubuntu computer, mkusb is likely the most suitable USB creation tool for you.
It builds a bootable flash drive with a FAT32 boot partition, thus booting BIOS or UEFI.
There is a ISO9660 read only secure OS partition. There is no need to encrypt this partition as it is standard unmodified OS.
The casper-rw Persistence partition offers persistence only limited by flash drive size.
A NTFS usbdata partition is usable for data on Linux or Windows computers.
Mkusb offers options to backup and restore the home directory, Wipe and restore the USB, write bootable images to USB, and has a Windows installer.
The home directory may be encrypted using standard encryption software.
https://help.ubuntu.com/community/mkusb
If you are restricted to Windows, YUMI makes a good persistent flash drive, however I have not tried encryption with a YUMI drive. It's casper-rw file is different than most.