Helping to make creation of nano-sized structures more user-friendly, scientists have designed single-stranded DNA and RNA (ssDNA and ssRNA) that can fold into desired shapes on command, and at an unprecedented scale. Their single-stranded inventions, in comparison to the more common double-stranded versions (where short "staple" strands fold a much longer strand into a shape), offer greater potential for increasing cost efficiency, large-scale production, and adaptability of shape-shifting polymers in nanotechnology. Many examples of information-carrying, self-folding molecules exist in the biological world, such as proteins that restructure into various shapes to gain new function. Bioinspired synthetic efforts to construct such molecules have been demonstrated with multi-strand DNAs and RNAs that use complementary base-pairing to self-fold, but progress on designing large molecular shapes using single-stranded DNA or RNAs (which don't have complementary strands to help drive folding motion) has been limited. Now, tackling the challenge of creating more complex, programmable, replicable and knot-free self-folding ssDNA and RNA, Dongran Han and colleagues have presented multi-kilobase DNA or RNA ssOrigami that could fold into 18 different structures, such as a rhombus, rectangle, square, smiley face and heart - all programmed with a user-friendly software tool. The ssOrigami self-configured smoothly into shapes as large as 10,682-nt ssDNA (37 times larger than previous largest ssDNA structures) and 6000-nt ssRNA (10 times larger than previous ssRNA structures). As well, various ssOrigami shapes could be successfully cloned and amplified inside living cells, such as Escherichia coli, representing a low-cost, high-scale production strategy for manufacturing the nanostructures.