Welcome to our Cell + Gene Curator roundup
Hot topics in the field this month include using CRISPR to engineer cell therapies and recent advances in bioengineering – key to unlocking the potential of regenerative medicine and tissue fabrication
James Strachan | | Quick Read
Walter Isaacson writes about people who change the world. His biography of Franklin shows how he brought together the passionate Adams brothers, the rectitudinous Washington, and Jefferson and Hamilton's intellects to create the Constitution and Declaration. Similarly, his book on Steve Jobs shows his lasting impact on cell phones, personal computers, music, publishing, retail – the list goes on.
So it's telling that his next subject is none other than Jennifer Doudna – who, along with Emmanuelle Charpentier, won the Nobel Prize in Chemistry for her role in developing CRISPR. From what I've heard, The Code Breaker details Doudna's remarkable personal story, as well as discussing the future implications for gene editing.
"Suddenly after a billion years of evolution one species had the talent and also the temerity to edit its own genes – to hack its own evolution," said Isaacson.
Deciding, as a species, what we're going to do with CRISPR may be the defining issue of this century. But, let's not get wrapped up in sci-fi dystopias and focus instead on the significant positives: the end of debilitating diseases.
Engineering the future of oncology
A current trend is using CRISPR to engineer cell therapies. For example, AbbVie has entered into a collaboration with Caribou Biosciences – which will use its CRISPR gene editing platform to engineer off-the-shelf CAR T cells with the ability to withstand host immune attack (1). AbbVie will then continue the programs into clinical development and commercialization. Let’s see if the deal – worth $40 million upfront and up to $300 million in milestone payments – will bear fruit as quickly as AbbVie's 2018 deal with CALIBR, which has already led to clinical trials (2).
Another example in the research comes from Guangxi Medical University: a team there recently used CRISPR to design nanobody-based anti-CD105 CAR T cells for solid tumors. The CAR T cells prolonged the survival time of tumor-bearing mice and human tumor xenograft models (3).
We’re also seeing a lot of improvements to the CRISPR system and new applications for the technology. Fred Hutch researchers developed "T cell optimized for packaging" (TOP) vectors for delivery of CRISPR-Cas9 to primary T cells that showed ~5–9-fold higher transduction efficiency than the commonly-used epHIV7 vector (4).
Meanwhile, Rice University researchers have developed a CRISPR/Cas9-based tool for editing the human epigenome – specifically histone phosphorylation. Their programmable chromatin kinase, called dCas9-dMSK1, allows for site-specific control over histone phosphorylation for the first time, and potentially opens the door to cracking the "histone code" – in other words, understanding how histones control gene expression. The researchers were also able to use dCas9-dMSK1 to identify seven new genes linked to melanoma resistance (5).
And in a brief departure from cell and gene therapy news, researchers from Columbia University in New York are using CRISPR to encode binary data into bacterial cells. By assigning different arrangements of DNA sequences to different letters of the alphabet, the team were able to encode the 12-byte text message “hello world!” into DNA inside E. coli cells. "This work establishes a direct digital-to-biological data storage framework, and advances our capacity for information exchange between silicon- and carbon-based entities," said the study authors (6).
Mighty morphin' biomaterials
Elsewhere, a number of advances have been made in biomaterials and 3D printing for regenerative medicine. A Northwestern University team has discovered a new printable biomaterial that mimics the properties of brain tissue. In 2018, the group reported the phenomenon of molecular reshuffling, where molecules migrate over long distances and self-organize to form larger, "superstructured" bundles of nanofibers. Now, they've shown that these superstructures can enhance neuron growth (7). The ultimate aim is to grow healthy neurons from a patient’s own cells using these superstructure-enhanced biomaterials, and transplant them into the brains of patients with neurodegenerative conditions.
In a related story, researchers at the University of Illinois at Chicago describe their new bioengineering material as "4D", which means it changes shape over time in response to stimuli – it can morph multiple times in a preprogrammed fashion or in response to external trigger signals. And that could allow the researchers to engineer tissue architectures that more closely resemble native tissues (8).
Finally, Carnegie Mellon University researchers have developed a new 3D-bioprinting method that could enable the fabrication of adult-sized tissues and organs (9). The Freeform Reversible Embedding of Suspended Hydrogels (FRESH) approach involves a yield-stress support bath that holds bioinks in place until they are cured. This prevents distortion of bioinks, which results in a loss of fidelity – a major barrier to advanced tissue fabrication.
This article is based on a selection of the breakthroughs that have recently been featured inThe Cell + Gene Curator - a weekly newsletter covering the latest news and research in the cell and gene therapy space. Subscribe for free at: https://www.texerenewsletters.com/cellandgene
- Caribou, “AbbVie and Caribou Biosciences Announce Collaboration and License Agreement for CAR-T Cell Products” (2021). Available at: https://bit.ly/3bjs5y7
- Scripps Research, “Calibr’s ‘switchable’ CAR-T platform for cancer moves forward with FDA clearance of Investigational New Drug application” (2020). Available at: https://bit.ly/3uV1wal
- F Mo et al., “Nanobody-based chimeric antigen receptor T cells designed by CRISPR/Cas9 technology for solid tumor immunotherapy” (2021). Available at: https://go.nature.com/3ebSwrB
- Fred Hutch, “TOP delivery of CRISPR-Cas9 machinery to primary T cells” (2021). Available at: https://bit.ly/3sMPHRy
- J Li et al., “Programmable human histone phosphorylation and gene activation using a CRISPR/Cas9-based chromatin kinase” (2021). Available at: https://go.nature.com/30ecEBd
- SS Yim at al., “Robust direct digital-to-biological data storage in living cells” (2021). Available at: https://go.nature.com/3edOgb8
- AN Edelbrock et al., “Superstructured Biomaterials Formed by Exchange Dynamics and Host–Guest Interactions in Supramolecular Polymers” (2021). Available at: https://bit.ly/3uUSUjX
- A Ding et al., “Cell‐Laden Multiple‐Step and Reversible 4D Hydrogel Actuators to Mimic Dynamic Tissue Morphogenesis” (2021). Available at: https://bit.ly/2PCt4kJ
- DJ Shiwarski et al., “Emergence of FRESH 3D printing as a platform for advanced tissue biofabrication” (2021). Available at: https://bit.ly/30ibfcA