Full Press Release Details
Wyss Institute Partners with Cellectis to Recode the Human Genome
project will use Cellectis' TALEN gene editing technology to create
first virus-resistant human cells for manufacturing therapeutics and
developing new cell-based therapies
BOSTON & NEW YORK--(BUSINESS WIRE)--May 1, 2018--Regulatory News:
Today the Wyss Institute for Biologically Inspired Engineering at
Harvard University and Cellectis (Paris:ALCLS) (NASDAQ:CLLS) (Euronext
Growth: ALCLS - Nasdaq: CLLS) a clinical-stage biopharmaceutical company
focused on developing immunotherapies based on gene-edited allogeneic
CAR T-cells (UCART), announced that they will collaborate to further
advance the Wyss Institute's efforts to recode the entire genome of cell
lines derived from humans and other species, and to develop new tools
and methods facilitating this goal. The cell lines would be engineered
to resist debilitating viral infections while carrying out their normal
functions, or even perform entirely new functions.
The Recode project lays the technical foundation to extensively and
functionally modify existing genomes in cells and whole organisms, and
aims to convert them into research tools as well as clinical and
biotechnological products.
The collaboration project was announced at the May 1 Genome
Project-write 2018 Scientific Working Meeting, conducted by the Center
of Excellence for Engineering Biology, as part of the first grand-scale,
community-wide GP-write project to develop such ultra-safe cells.
Previously, the group of George Church, Core Faculty member at the Wyss
Institute, Professor of Genetics at Harvard Medical School (HMS) and of
Health Sciences and Technology at Harvard and the Massachusetts
Institute of Technology (MIT), published on efforts to radically recode
the bacterium E. coli's genome. The researchers reduced the
number of codons - the sequence units in the DNA that encode the amino
acids the bacterium's proteins are composed of - from 64 to 63. This
caused the recoded bacteria to become resistant to most viruses and to
be biocontained' in their intended laboratory environments since their
survival can be linked to chemicals not found in the wild.
Building on these accomplishments, Church said, "The Recode project will
create ultra-safe human cells that are resistant to infection with all
viruses and prions. These cells and the technologies we are developing
along the way will enable more effective ways to manufacture protein
therapeutics, vaccines, cell therapies and transplantable organs."
Under the collaboration with Cellectis, Church and his team will be
given access to the company's TALEN gene editing technology. TALEN,
short for transcription activator-like effector nucleases, are genome
engineering enzymes that can introduce changes into the DNA code with
high specificity and across an entire genome, and they can be
multiplexed to make multiple changes at a time. "In the Recode project,
our capabilities to edit genomes and invent new tools for high-level
multiplexing of these efforts perfectly align with Cellectis' expertise
and strengths. Cellectis' TALEN gene editing technology will contribute
much to the success of this project," said Church.
All protein-coding DNA sequences in a cell's genome consist of triplet
codons containing three of the four basic nucleotide bases known in
shorthand as A, T, G and C. In addition, the beginning of a
protein-coding DNA sequence is signaled by a START codon and its end
with a STOP codon to enable the appropriate translation of DNA into the
proteins' amino acid sequences. As most amino acids are redundantly
encoded by two to six triplet codons, Church and his team seek to
compress the codon usage for specific amino acids from six down to four
To achieve this, the team will deploy sequence-tailored TALEN enzymes
to help modify codons at 400,000 locations across the protein-coding
regions of the human genome. The lab can then delete the genes encoding
the RNA molecules known as transfer RNAs that the cells previously
required during their protein synthesis to add amino acids corresponding
to the eliminated codons.
"We are looking forward to collaborating with the Wyss Institute and
George Church's group on this very exciting Recode project using
Cellectis' technology to recode the entire genome of human and other
species cell lines," said Dr. Andr Choulika, Chief Executive Officer of
Cellectis. "The precision, the performance and the flexibility of TALEN
technology makes it the optimal gene editing platform for such a
cutting-edge project."
This simplification of the protein-encoding portion of the genome can
prevent viruses, which need the full repertoire of codons to produce
their own proteins, from hijacking the host cells' protein-synthesizing
machinery. It will also allow researchers to re-purpose eliminated amino
acid codons for the incorporation of nonstandard synthetic amino acids
that can enable new protein functions and provide a reliable means for
containing recoded cell lines in laboratory or industrial environments.
"The Recode project and partnership between synthetic biologists at the
Wyss Institute and Cellectis represents a major new application area for
genome engineering that could open up entirely new paths for prevention
of infectious disease, as well as for biomanufacturing, organ
transplantation, and regenerative medicine," said Wyss Institute
Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah
Folkman Professor of Vascular Biology at HMS and the Vascular
Biology Program at Boston Children's Hospital, as well as Professor of
Bioengineering at the Harvard John A. Paulson School of Engineering and
About the Wyss Institute for Biologically Inspired Engineering at
Harvard University (http://wyss.harvard.edu). The Wyss
Institute for Biologically Inspired Engineering uses Nature's design
principles to develop bioinspired materials and devices that will
transform medicine and create a more sustainable world. Wyss researchers
are developing innovative new engineering solutions for healthcare,
energy, architecture, robotics, and manufacturing that are translated
into commercial products and therapies through collaborations with
clinical investigators, corporate alliances, and formation of new
startups. The Wyss Institute creates transformative technological
breakthroughs by engaging in high risk research, and crosses
disciplinary and institutional barriers, working as an alliance that
includes Harvard's Schools of Medicine, Engineering, Arts & Sciences and
Design, and in partnership with Beth Israel Deaconess Medical Center,
Brigham and Women's Hospital, Boston Children's Hospital, Dana-Farber