Harvard Scientists Discover New Method for Creating Biological Polymers

Professor David R. Liu ’94 and coworkers have reported a new synthetic method of directly building polymers by reading the genetic code off of DNA. According to Liu, this method could eventually lead to the discovery of useful new biological compounds.

The human body constantly reads genetic code off of DNA, otherwise know as deoxyribonucleic acid, onto RNA, or ribonucleic acid, and then uses ribosomes, cellular structures, to translate genetic code and build a chain of amino acids linked in a specific order. These molecular chains are called proteins. Because proteins are comprised of a series of linked molecular units, they are examples of molecular chains called polymers.

“The idea of trying to turn the information in DNA sequences into materials other than proteins has been an aspiration of chemists and chemical biologists for quite some time,” said Liu. “Previous efforts to use DNA to direct polymer synthesis have largely been limited to the synthesis of nucleic acids or nucleic acid-like polymers, such as DNA, RNA, or peptide nucleic acids, or PNA.”

This study, published in the journal Nature Chemistry, demonstrates for the first time a method of creating entire non-nucleic acid polymers directly from the code on DNA. Previously, non-nucleic acid polymers had to be built stepwise, by adding one new unit to the polymer’s end each time. In this method, building a ten-unit polymer would take ten separate steps. Using Liu’s method could reduce the number of steps and the time required.

“Biological polymers have many special properties, such as the ability to catalyze chemical reactions, to fold into specific shapes, and to have specific dynamic properties because of their precise sequence-defined structure,” Liu said. “Just like beads on a string, each building block is installed in a precise order to generate a biological polymer.”

The technique presented by Liu’s team works by attaching a piece of specifically coded PNA to a building block of a biological polymer. In this way, each unit of one type can be identified by a short PNA code. Several different PNA-labeled building blocks are then introduced into a system with DNA templates, which have been coded to match the PNA labels and order them precisely. Thus, the DNA lines up each separate building block in a sequence-defined order so the polymer chain is primed for attachment in one step.

Building such polymers is relatively easy due to the structural similarity of DNA and other nucleic acids, allowing them to bind naturally in a specific order. Using PNA “adapters” to bind these building blocks, Liu used a coded strand of DNA to put together any family of linkable blocks, regardless of structure.

Liu stated that the implications of this work lie in the ability to create libraries of millions or billions of these polymers and DNA templates more efficiently. Having these libraries would facilitate evolving these polymers. Liu’s group plans to screen these polymers for desirable properties, such as activation of certain genes, in a process that he said will approximate Darwinian evolution.