• Inscripta is committed to responsible, safe use of its digital
genome engineering technology.
• Genome engineering presents biosecurity challenges, some
distinct from other areas of synthetic biology.
• A call for a collaborative approach to address biosecurity
challenges for genome engineering
Inscripta’s technology and products enable digital genome
engineering on an unprecedented scale
Effective solutions require:
• Unprecedented SCALE
• Superior PERFORMANCE
• Greater ACCESS
Number of Genomic Locations
102 103 104
Number of Edits
Onyx™ Digital Genome Engineering Platform
Inscripta Engineering Portal
Generates up to 10k precisely engineered libraries of single cells at
Inscripta’s mission is to avail these tools to the public
Inscripta is committed to safe use of its
Biosecurity processes help prevent malicious or accidental production of
potentially harmful organisms
Genome and Edit library
screening identifies potential
biothreat before production
Editing library kits
known bad actors
Customer designs edits
in own lab on approved
genome of choice
Inherent controls prevent
unauthorized use of MADzymeTM
nucleases and OnyxTM platform
Customer creates edits,
carries out genotyping
and phenotyping in own lab
Genome engineering biosecurity considerations overlap and diverge
with other synthetic biology technologies
Broad biothreat space
Features Unique to
Edits must be considered in the context of the genome
and cell behavior
o Regulatory sequence
o Protein interactions
Scale issues for massively parallel genome editing
o Multiple edits per cell will add complexity
Collaboration is needed across Synthetic Biology AND amongst the Genome Engineering
community to address Biosecurity challenges
Genome engineering biosecurity must consider cellular context and
enormous phenotypic diversity
Each edit variant
must be evaluated
within cellular context
for biothreat potential
Libraries of cells with
Edits can alter the function or
expression of an individual protein,
which in turn may
have numerous cellular effects
Community-based strategy to strengthen genome engineering
biosecurity and minimize biorisk
Define biosecurity ‘best practice’
standards for genome engineering
Strategize to close resource gaps:
research, DBs, test sets
Instill societal confidence in genome engineering;
protect the bioeconomy
Recruit support from government,
Share ideas and resources
Collectively address ‘challenges’
The unique challenges of biosecurity for genome engineering requires collaborative problem solving
Let’s Work Together!
10. • Source here
of Biology to
Natural Products Pharmaceuticals Buildings
And Must Be
Thank you to Catalyst, I feel honored to participate in this landmark event and proud to represent Inscripta here.
Today will talk a bit about inscripta’s commitment to biosecurity for responsible, safe use of its digital genome engineering technology.
Then I will describe how the power of Genome engineering to accelerate biological discovery presents biosecurity challenges, some distinct from other areas of synthetic biology.
Will end with a call for a community-based strategy to address and solve our problems, establish Biosecurity ‘Best Practices’ and promote societal trust in this rising technology
Inscripta enables Genome engineering on unprecedented scale
How does this work?
leading strategy for scientists to make biological discoveries Is to study the effects of genomic perturbations
Historically, these genomic changes have occurred through natural evolution or deliberately through various methods of mutation and engineering. Some approaches have strengths in targeting numerous loci across the genome with huge numbers of edits, however, limited by edit type. Other approaches, here on the Y axis have advantage of allowing a variety of edit types, single base pair or codon changes, insertions/deletions, promoter swaps, focused edits on area of interest such as protein engine,.. Yet remain limited to discrete regions of the genome. Trade off. Inscripta’s innovative chemistry pulls us into this outer quadrant to dramatically increase the genotypic assortment and thus phenotypic diversity that can result from a single experiment. Hence the scale like we’ve never seen…chemistry and protocols provide superior performance. Access is important to Inscripta
And our mission is to make these tools widely available to any one who seeks this unbound biological exploration. Onyx platform gives this awesome power to customers. Suite of instrument, software and reagents in the customers own lab which is where they carry out the iterative design, generate, test ,and learn cycle, each round zoning in on key breakthroughs in their own research or product development. Customer empowerment facilitates high impact discoveries, yet must be addressed in Biosecurity system.
With Biosecurity a priority, Inscripta proactively implement screening processes with a goal to identify and help prevent deliberate or accidental production of a biorisk
Here we underlie biosec controls unto the customer ‘journey’ to discovery
Since customer directs their own edits, we follow standard protocols to screen out known bad actors upfront, unlikely, yet non-zero
Edit library kits are produced at Inscripta, and likewise we have inhouse screening processes designed to rapidly identify potential biothreat invoking sequence before reagent production.
The kits are shipped to customers to carry out the genome engineering in their own lab. Biosecurity is upheld though through various inherent controls. For example the use of ‘barcodes’ on reagents to prevent unauthorized and unscreened use.
Inscripta Enables and inspire others to be first to make break through discoveries. We are committed to ensuring SAFE use of this customer-centric technology
However, as we have developed our biosec system, we have encountered challenges that are unique to GE, as well as addressed biosec features shared across synbio
As we are discussing here today Biosecurity in synBiology requires inclusive, ongoing dialogue across the industry.
Shared Bioscurity needs include upfront customer screening, identif of biothreat across a broad space, and proactive reporting protocols to avoid ad hoc, poorly planned reactive responses
Let’s look at biosec considerations thst GE brings to us::
The advantage of high-throughput genome wide engineering to capture enormous phenotypic diversity has a flip side The potential functional impacts of edits on cell behavior are complex and we must consider regulatory effects and protein interactions. Scale issues result from the huge numbers, esp when multiple edits/cell. Wow! This is getting complicated. These phenomena are conceptualized on the next slide so we can take a closer look.
Continued communication across synbio is important, yet we also need collaboration within the GE community to address these novel challenges
This cartoon represents how key strength of genome engineering, the enormous scale of phenotypic diversity that may be probed, also underlies its major biosecurity dilemmas. The functional effect of a given edit in say, an Ecoli genome, may alter multiple cell processes. Even if a cell has only one edit, whether it be to a regulatory region that affects expression of one or more proteins, or a coding region that changes the shape of a single protein, the protein interactions and pathways that could be altered may be complex, and difficult to predict.
Multiply this times libraries with up 1000s cells, the range of functional effects and emergent properties resulting from a typical experiment could be huge. Rigorous Biosecurity ought to evaluate each variant in genomic context
Furthermore as technology advances, multiple edits/cell, or combination editing, will result in an exponential increase in number of variants. Yikes! A clever systems biology approach will be needed to evaluate the enormity of edit variant combinations within cellular context
Clearly, predicting biothreat of genome wide engineering is daunting!
Yet there is hope, as we are gathered for this event, we appreciate that with a community based strategy, we can begin to tackle these biosecurity challenges through open minded dialogue and collaborative problem solving
Inscripta is rising to this challenge yet want this to be a community-driven.
How can a community, with a common interest in GE, work together to prioritize and strengthen its biosecurity. Sharing ideas
important to define Best Practices, set norms and standards. In order to do so, we will need to meet resource gaps. Research to help develop curated DBs, and complex sequence sets needed to test screening algorithms. Compilation of phenotypic results to help predict emergent properties
we need to address biosecurity challenges, as a group, pursue support from other stakeholders, help influence legislation and acquire needed resources
We recognize the vast benefits of GE across numerous sectors, thus major contributor to Bioeconomy, it will be critical to Communicate the truth about the benefits and risks of GE to the public, to instill societ trust and protect Bioeconomy
Genome Engineering technology must thrive since The POWER of Biology is PROFOUND. As scientists are equipped to explore biological systems at an unprecedented scale, we are better positioned to solve some of society’s most pressing problems.
Yet as access and scale of this technology expands, we must continue to work together to respect and protect the power of Biology.
Discussion Qs: (need one for small groups in audience to discuss)
What do you foresee as the most daunting GE specific Biosecurity challenge, and how might we strategize addressing it? (last half might be too much for this situation)
What biosecurity related topics are most critical for the Genome Engineering community to address
What concerns do you have about the kinds of large-scale genomic engineering that the Onyx represents