Dataset Information

The Cancer Cell Target Discovery. Comparing Laboratory Evolution of Expanded DNA Six-Nucleotide Alphabets with Standard Four-Nucleotide Alphabets

ABSTRACT: Artificial evolvable genetic information systems (AEGIS) are DNA-like molecules that can be copied, support laboratory in vitro evolution (LIVE), and evolve to give AegisBodies, analogs of antibodies. However, unlike DNA aptamers built from four different nucleotides, AegisBodies are built from six. Thus, 6-letter AEGIS-LIVE delivers AegisBodies with greater stability in biological mixtures, more folds, and enhanced binding and catalytic potential. However, AEGIS has not benefitted from four billion years of biological evolution. To learn whether AEGIS can nevertheless perform as well as natural DNA, we compare two 6-letter AegisBodies (LZH5b and LZH8) with a standard 4-letter aptamer. Both were evolved to bind cancer cells after ~10 cycles of LIVE. Both have ~ 50 nM affinities. Both discovered proteins on their cancer cell surfaces thought to function only inside of cells. Both can be internalized. Internalizing of LZH5b attached to an AEGIS nanotrain brings attached drugs into the cell. These data show that AEGIS-LIVE can do what 4-letter LIVE can do at its limits of performance after four billion years of evolution. However, synthetic biologists continue to improve AEGIS, suggesting that AEGIS not be dismissed as an avenue for future biotechnology.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Liver Cancer

SUBMITTER: Sharpkate Shaker

LAB HEAD: Liqin Zhang

PROVIDER: PXD055107 | Pride | 2025-05-07

REPOSITORIES: Pride

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Cancer cell target discovery: comparing laboratory evolution of expanded DNA six-nucleotide alphabets with standard four-nucleotide alphabets.

Shaker Sharpkate S Li Jun J Wan Shuo S Xuan Hong H Long Jinchen J Cao Haiyan H Wei Tongxuan T Liu Qinguo Q Xu Da D Benner Steven A SA Zhang Liqin L

Nucleic acids research 20250201 4

Anthropogenic evolvable genetic information systems (AEGIS) are DNA-like molecules that can be copied, support laboratory in vitro evolution (LIVE), and evolve to give AegisBodies, analogs of antibodies. However, unlike DNA aptamers built from four different nucleotides, AegisBodies are currently built from six different nucleotides. Thus, six-letter AEGIS-LIVE delivers AegisBodies with greater stability in biological mixtures, more folds, and enhanced binding and catalytic power. Unlike DNA how ...[more]

PMID: 39950344

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	A14_1.msf	Msf
	A14_1.pdResult	Other
	Data_Based_Search_Results.zip	Other
	RAW.zip	Other