Cryo-EM: What Level of Outsourcing is Right for You?

Is Cryo-EM right for you?

Cryo-electron microscopy (cryo-EM) is a uniquely powerful method used to obtain detailed structural information about proteins and is rapidly emerging in the field of structure-based drug design. However, adopting cryo-EM is a big step, requiring significant upfront investment. 

With service providers offering a wide range of support, you can choose to outsource some (or all) of your cryo-EM project. Here, we delve into the factors to consider when deciding which working style is the best choice for your group, and the pros and cons of each level of outsourcing.

What it takes to adopt cryo-EM in your laboratory

A laboratory’s first ever cryo-EM structure is typically a labor of love, motivated by the benefits of enabling structure based drug design for the first and subsequent targets of interest. While adopting cryo-EM and tackling new methodology may be daunting, partnering with the right experts can help you get started. For some laboratories, embarking on a proof-of-concept project may be a good initial step. For more details, see our previous post on adopting cryo-EM in your drug discovery program. 

Gauging internal demand

How many cryo-EM projects are you likely to tackle each year? Asking this simple question is a great starting point; if there is a consistent internal demand for the technology and on-site expertise the initial investment will eventually pay off. In this case, i.e., for large laboratories with a half a dozen or more projects per year, setting up an in-house cryo-EM suite could be a viable option.

On the other hand, if you are expecting 3-4 cryo-EM projects each year, outsourcing would probably be the best option to get started quickly, reduce upfront investment and avoid delays in your drug discovery pipeline.

Considering the value of a collaborative partnership

Outsourcing or partnering with cryo-EM specialists can help you cut upfront costs – rather than invest millions, you can instead pay per project, or per unit of access. Collaborating with an experienced partner also helps ensure you have all the support needed for iterations and optimization at every step. This can be particularly beneficial when you are embarking on your first cryo-EM-based project and want extra support to help your project take off successfully.

If intellectual property (IP) and time-to-structure are critical considerations for your team, you might want to prioritize selecting a partner that can offer strict confidentiality and accommodate fast-paced timelines.

In-house vs. outsourcing: Exploring the spectrum of options

Complete outsourcing: permanently or temporarily

You might choose to outsource all of your cryo-EM work on a permanent basis. In doing so, you remove the need for capital investment, ongoing support and service cost, and gain quick access to expert sample preparation, data collection techniques and analysis.

Alternatively, temporarily outsourcing your cryo-EM projects can give you an opportunity to complete a proof-of-concept study before making a bigger commitment.

If you choose to outsource, either temporarily or permanently, be aware that your timeline becomes dependent on your partner’s schedule, and you may need to consider IP protection.

Partial outsourcing

A range of options lie between the extremes of in-house and outsourcing. You may choose to:

• Outsource high-resolution data collection (with sample preparation and screening completed in-house)
• Outsource screening and high-resolution data collection (with sample preparation completed in-house)

Outsourcing specific stages of the workflow reduces some of the costs associated with implementing cryo-EM. Furthermore, you can perform proof-of-concept studies quickly to test projects using minimal resources, while having the flexibility to experiment with different sample preparation and screening approaches. As with full outsourcing arrangements, you will need to consider IP protection and the implications of relying on your partner’s schedule for project completion. Additionally, you will have to absorb some of the major expenses associated with implementing a cryo-EM workflow. A mixed in-house and outsourcing model may be particularly convenient if you are intent on adopting a full cryo-EM suite in the future; as the projects start to increase and further investment is justified, you can transition towards a full internal investment.

Complete in-house pipeline

As described in our prior post, there are benefits to making the leap to adopt a complete cryo-EM suite, particularly if your assessment of internal needs merits the investment. Benefits center around more internal control, with the possibility of more flexible and rapid turnaround, depending on your organizational structure.  

Undeniable benefits of cryo-EM – regardless of your strategy

No matter where you sit on the in-house vs. outsourcing spectrum, investing in a cryo-EM platform can help you take your structure based drug design to the next level. Gaining the capability to unravel previously inaccessible drug discovery targets gives you a competitive edge and ultimately can reduce the time and cost of bringing a molecule to the clinic.

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