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In other words, can you update the spine tag with a script instead of converting to zip, opening, and replacing? Thanks.

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Create an epub3 book or convert your existing epub2 book to an epub3 book and add a page-progression-direction="rtl" attribute to the <spine> tag in the content.opf file.

You can convert epub2 books to epub3 books with Calibre. (Polish books ▶ Upgrade book internals.)

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