National

Bioengineers discover reverse translation technique

by Claudia Casal Montserrat
Games Editor

Ever since Francis Crick’s discoveries in the 1960s, scientists have widely accepted how proteins are made: they are translated from RNA which is transcribed from the fundamental genetic code, DNA. This central dogma of biology was just challenged in March.

Bioengineers at Stanford designed a chemical reaction to convert proteins into their matching DNA sequences. Although, this isn’t the first time that the central dogma of biology has been expanded upon. In 1970, both Howard Temin and David Baltimore found reverse transcriptase in Rous sarcoma and murine leukemia viruses. Reverse transcriptase allows for DNA to be made from RNA, and allows for millions or billions of copies of DNA to be made inexpensively and quickly.

Their work won Temin and Baltimore the noble prize as well as paved the way for identifying retroviruses—viruses that rewrite their DNA into their host’s genome, like HIV and AIDS— and reverse transcription-polymerase chain reaction (RT-PCR). PCR, a technique also performed in a Los Gatos High School biology lab, is a process that allows scientists to make billions of copies of DNA, which is used to test for genetic diseases as well as being essential for the sequencing of the human DNA in the Human Genome Project. RT-PCR is a similar process in which RNA is converted into DNA that can be used to detect viruses, study gene activity, and diagnose diseases. 

Liwei Zheng and his team found the most recent discovery: reverse translation. Proteins are the machinery of cells and are incredibly complex and diverse: there are 10,000 to 100,000 distinct proteins in the human body. This invention works by tagging individual amino acids with a DNA barcode specific to each protein, allowing synthetic DNA to encode the protein. This breakthrough requires an extremely small amount of protein, allowing this technology to be used to identify and sequence rare proteins.

Proteins have long been a challenge to sequence because of the 20 smaller amino acids they are made from (compared to the four nucleic acids that DNA and RNA are made of). Describing his discovery, Zheng said, “What really is different is how much from the same sample we can see…With mass spectrometry, you’re shooting 1 billion to 10 billion protein molecules and see, typically, a million molecules out of it. With our method, you can potentially see 1,000 times that amount.”

Although this technique still needs to be optimized and made widely available, it can be used to better understand cellular functions, rare proteins, and cancer. In medicine, this technology could allow for extremely sophisticated diagnostics, making mRNA vaccines more efficiently, and inexpensively sequencing proteins.

Sources: (Nature Biotechnology, NIH, and Stanford Reports)

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