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April 2023 Progress Update
Overcoming a primary challenge
What were we up to in March?
In lieu of a written update for March 2023, we held a live Progress Update event at NewLimit HQ in South San Francisco. Check out the recording here for a quick summary of progress in our first few quarters: livestream.newlimit.com
NewLimit is developing therapies that reprogram cell age without changing cell type. To achieve this ambitious goal, we’re building screening technologies that enable us to test many reprogramming strategies for their ability to make old cells “look” young.
In April, we performed our first reprogramming screens in primary human T cells, bringing us a step closer to finding an impactful reprogramming strategy.
Alongside experimental progress, we also welcomed two new members to our team:
Both John & Jenny will be joining our Immunology team focused on developing high-throughput functional assays and gold-standard pre-clinical models.
A few highlights from our work this month:
Partial reprogramming screens in primary human T cells
In April, we completed our first partial reprogramming screen in human T cells taken from healthy young and old donors. Similar to our screens in a cell line model from February and March, we were able to test hundreds of reprogramming combinations simultaneously.
We believe this is the largest partial reprogramming screen in primary cells that has been performed. Not only does it demonstrate that the NewLimit Discovery Engine can be applied to primary cells, but these are also the first data where we can being to ask — which partial reprogramming interventions make old cells look younger?
While it may seem like a small step to move from a cell line to real, human T cells, it was technically challenging. Every step of the process from gene delivery, to reprogramming induction, to cell profiling required optimization to work in primary cells. We’re incredibly proud of our team for pushing through the technical hurdles.
Prioritizing transcription factors for partial reprogramming screens
Now that our reprogramming screens are up and running in primary cells, a natural question arises — what partial reprogramming factors should we test?
Our Predictive Modeling team set out to answer this question quantitatively this month. They’ve nominated our first expanded set using a diverse collection of sources: existing data on functional effects in primary T cells, our own internal epigenetic aging maps, gene activity covariance during ontogeny, and our predictions from our own internal TF → Function prediction models.
Along the way, we’ve made some of our first open source contributions back to the community. Thanks to the
scvi-toolsteam for a collaborative development process!
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