Level 1 — Absolute Beginner

Every living thing on Earth uses DNA. DNA is a code, and it is made of only 4 letters: A, T, C, and G. These 4 letters tell your body how to grow and work.

Now scientists made a new kind of DNA. It has 8 letters, not just 4! This special DNA is called Hachimoji DNA. Hachimoji means eight letters in Japanese.

A scientist named Dong Wang led a team at UC San Diego. They wanted to know if a normal cell part, called an enzyme, could read this new 8 letter DNA. The enzyme is called RNA polymerase. It usually reads only the natural 4 letters.

The team used a powerful tool called cryo-electron microscopy to look very closely. They saw that the enzyme could read the new letters almost the same way it reads the old ones. This is exciting news for science and medicine in the future.

DNA

The molecule inside cells that carries the instructions for life.

Enzyme

A tiny helper made by cells that does a special job.

Letter (genetic letter)

A basic unit of the DNA code, like A, T, C, or G.

Alphabet

A full set of letters used to write a code or language.

RNA polymerase

An enzyme that reads DNA and copies it.

Synthetic

Made by people, not found naturally.

Microscope

A tool that makes very small things look big enough to see.

Biotechnology

Using living things or their parts to make new products or tools.

Level 2 — Elementary

Every living creature on Earth, from bacteria to humans, stores its genetic information using DNA, a molecular code built from just 4 chemical letters: A, T, C, and G. For decades, scientists have wondered whether life's code could be expanded beyond this natural set.

Researchers have now created a synthetic DNA system with 8 letters instead of 4. It is called Hachimoji DNA, and it adds 4 new, human made letters to the original 4 found in nature.

A research team led by Dong Wang, a professor at the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, wanted to test something important: could an ordinary enzyme from a living cell actually read this expanded alphabet? They studied RNA polymerase, an enzyme taken from E. coli bacteria, whose normal job is to read DNA and copy it into RNA.

Using a high resolution imaging method called cryo-electron microscopy, the team discovered that the enzyme recognized the new synthetic letters almost as well as it recognizes the natural ones. Their results were published on September 2, 2026, in the journal Nature Communications, and mark a promising step toward future tools in biotechnology and medicine.

Genetic code

The set of instructions, written in DNA, that tells a cell how to build and run a living thing.

Synthetic biology

A field of science that designs new biological parts or systems that do not exist in nature.

Enzyme

A protein that speeds up or carries out a specific chemical task inside a cell.

RNA polymerase

An enzyme that reads a strand of DNA and builds a matching strand of RNA.

Transcription

The process of copying information from DNA into RNA.

Cryo-electron microscopy

An imaging technique that freezes molecules and uses electrons to reveal their detailed structure.

Base pair

Two matching genetic letters that join together to form a rung of the DNA ladder.

Nucleotide

A basic building block of DNA or RNA, made of a sugar, a phosphate, and a genetic letter.

Level 3 — Intermediate

All known life on Earth relies on an astonishingly narrow genetic vocabulary: just four chemical letters, adenine, thymine, cytosine, and guanine, arranged in countless combinations to encode everything from a bacterium's metabolism to a human brain. That narrowness has long raised a question for synthetic biologists: is the four letter alphabet a fundamental requirement of life, or simply the version evolution happened to settle on?

A team led by Dong Wang, PhD, of the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, has now shown that an unmodified, naturally occurring enzyme can accurately transcribe an expanded, laboratory made genetic alphabet of eight letters, known as Hachimoji DNA. The four additional synthetic letters were engineered to pair with one another much as the natural letters do, but until now it was unclear whether the cellular machinery of a real organism could actually process them.

The researchers focused on RNA polymerase, the enzyme within E. coli bacteria responsible for reading a DNA template and transcribing it into RNA, the essential first step by which genetic information becomes functional. Using cryo-electron microscopy, a technique that flash freezes molecules and images them with a beam of electrons to reveal near atomic detail, the team captured the enzyme in the act of engaging with the synthetic letters, and found that it recognized them through mechanisms strikingly similar to those it uses for natural DNA.

Published September 2, 2026 in Nature Communications, the findings suggest that ordinary biological machinery is not inherently restricted to the four letter code life has always used, a result with implications for encoding denser information in DNA and engineering new classes of molecules for medicine and biotechnology. Wang's team frames the work as evidence that expanding life's genetic vocabulary may be achievable without redesigning the cell's existing toolkit from scratch.

Nucleobase

One of the chemical units, such as adenine or a synthetic equivalent, that pairs with a partner to form the rungs of a DNA molecule.

Transcription

The cellular process by which an enzyme reads a DNA sequence and synthesizes a corresponding RNA molecule.

Synthetic genetic system

An engineered set of genetic letters, beyond the four found in nature, designed to expand what DNA can encode.

Structural biology

The scientific study of the three dimensional shapes of molecules and how those shapes determine function.

Cryo-electron microscopy

A structural biology technique that images flash frozen molecules with electrons to resolve their architecture at near atomic resolution.

Base pairing

The chemical pairing of two complementary genetic letters that holds the two strands of DNA together.

Cellular machinery

Level 4 — Advanced

For nearly four billion years, every organism on Earth has inherited the same modest genetic vocabulary: four nucleobases, adenine, thymine, cytosine, and guanine, whose pairings encode the entirety of biological complexity, from a microbe's enzymes to a symphony's composer. Whether that narrow alphabet reflects some deep biochemical necessity, or merely an evolutionary accident that life never had reason to outgrow, has remained an open and consequential question for the field of synthetic biology.

New research from a team led by Dong Wang, PhD, at the UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, offers a striking answer. The scientists demonstrated that an unaltered, naturally evolved enzyme, RNA polymerase drawn from E. coli bacteria, can faithfully transcribe Hachimoji DNA, a synthetic genetic system that doubles the natural alphabet to eight letters by adding four laboratory engineered bases alongside the familiar four.

Employing cryo-electron microscopy, a technique capable of resolving molecular architecture at near atomic resolution by imaging specimens flash frozen in a thin layer of ice, the researchers captured the enzyme engaging the synthetic bases and found that its recognition mechanisms closely mirrored those it deploys on ordinary DNA, a finding that was by no means guaranteed given how finely tuned such enzymes typically are to their natural substrates.

The results, published September 2, 2026 in Nature Communications, carry implications well beyond a single laboratory demonstration. If a cell's existing molecular machinery can process information encoded in an expanded alphabet without wholesale redesign, the path toward denser genetic data storage and engineered biomolecules for medicine grows considerably shorter, suggesting that the boundaries of life's code may be more negotiable than four billion years of precedent would suggest.

Nucleobase

A nitrogen containing molecular unit whose specific pairing chemistry underlies the storage and transmission of genetic information.

Substrate specificity

The tendency of an enzyme to act preferentially, or exclusively, on a particular molecule or class of molecules.

Molecular architecture

The precise three dimensional arrangement of atoms within a biological molecule that determines its function.

Synthetic genetic system

An engineered expansion of the natural genetic alphabet, designed to test or extend the informational capacity of DNA.

Cryo-electron microscopy

A structural imaging technique in which flash frozen specimens are visualized with an electron beam to achieve near atomic resolution without crystallization.

Evolutionary contingency

The idea that a biological feature arose from the particular historical path evolution took, rather than from strict necessity.