MIT Engineers program Human Cells to store complex Histories in their DNA.
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MIT Engineers program Human Cells to store complex Histories in their DNA.


MIT biological engineers have devised a way
to record complex histories in the DNA of human cells, allowing them to retrieve “memories”
of past events, such as inflammation, by sequencing the DNA. This analog memory storage system — the
first that can record the duration and/or intensity of events in human cells — could
also help scientists study how cells differentiate into various tissues during embryonic development,
how cells experience environmental conditions, and how they undergo genetic changes that
lead to disease. Many scientists have devised ways to record
digital information in living cells. Using enzymes called recombinases, they program
cells to flip sections of their DNA when a particular event occurs, such as exposure
to a particular chemical. However, that method reveals only whether
the event occurred, not how much exposure there was or how long it lasted. The researchers have previously devised ways
to record that kind of analog information in bacteria, but until now, no one has achieved
it in human cells. The new MIT approach is based on the genome-editing
system known as CRISPR, which consists of a DNA-cutting enzyme called Cas9 and a short
RNA strand that guides the enzyme to a specific area of the genome, directing Cas9 where to
make its cut. CRISPR is widely used for gene editing, but
the MIT team decided to adapt it for memory storage. In bacteria, where CRISPR originally evolved,
the system records past viral infections so that cells can recognize and fight off invading
viruses. When using CRISPR to edit genes, researchers
create RNA guide strands that match a target sequence in the host organism’s genome. To encode memories, the MIT team took a different
approach: They designed guide strands that recognize the DNA that encodes the very same
guide strand, creating what they call “self-targeting guide RNA.” The researchers also showed that they could
engineer cells to detect and record more than one input, by producing multiple self-targeting
RNA guide strands in the same cell. Each RNA guide is linked to a specific input
and is only produced when that input is present. In this study, the researchers showed that
they could record the presence of both the antibiotic doxycycline and a molecule known
as IPTG. Currently this method is most likely to be
used for studies of human cells, tissues, or engineered organs. By programming cells to record multiple events,
scientists could use this system to monitor inflammation or infection, or to monitor cancer
progression. It could also be useful for tracing how cells
specialize into different tissues during development of animals from embryos to adults.

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