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Gordian-Curated Highlights from ASGCT24

May 23, 2024

Reflections on an action-packed week in Baltimore

A college of Gordian employees spending time at a conference. With a logo overlay reading ASGCT Annual Meeting, 20204, Baltimore Maryland.
Seven Gordian Employees posing for a photo at a baseball stadium.

Five Gors descended on Baltimore last week for the 24th American Society for Cell & Gene Therapy Annual Meeting (#ASGCT24). As usual, we came back full of knowledge and inspiration, and thoroughly exhausted.

With thousands of attendees and many speakers and companies, there’s a massive amount of information to process. Following are highlights through the Gordian lens:

Progress Developing Therapies for Prevalent Disease

A number of companies shared promising trial results, including:

  • Sardocor’s phase 1 HFrEF clinical trial using AAV1
  • AskBio’s phase 1 clinical trial using AAV2i8 for congestive heart failure now moving to a phase 2 trial
  • Pacira Biosciences’ AAV2.5 ILR-1a trial in osteoarthritis
  • Korean gene therapy company @ICM Co Ltd’s phase 1 AAV5.2 Nkx3.2 osteoarthritis trial

Trends in AAV Innovation

  • Understanding AAV genomic integrations as both something bad due to off-target effects or potentially good for sustained expression
  • Understanding and engineering inverted terminal repeats (ITRs) – using natural AAVs and not just AAV2 ITRs, looking at the effects of deletion and proximal regions
  • Engineering capsids and promoters to de-target the liver for more specific gene delivery
  • Thinking outside of the box for improvements to AAVs
    • Cirsium Biosciences manufacturing AAVs in plants (!?)
    • Regeneron using antibody-conjugated AAVs as a platform

New Knowledge in AAV Manufacturing

  • New innovations in the AAV polishing step of removing empty capsids, with many people using the Sartorius CIM Monolith columns
  • More people are talking about partial AAVs (vectors with truncated genomes)! Spark Therapeutics showed purification of empty, partials, and fulls through oversaturated loading multicolumn AEX. People were excited about the Refeyn SamuxMP mass photometer as the instrument for AAV assays
  • Gordian has noticed vectors with truncated genomes as well, observing variable truncation rates depending on genome length, sequence, and structure. We found that charge detection mass spectrometry (CDMS) shows that prolonged exposure to acidic conditions causes viral genome extrusion
  • Lukas C. Bachmann and his team at the Salk Institute optimized a method to successfully package and express transcripts for large proteins in AAV through RNA-end joining. This is an important step forward for reliable expression of large proteins in gene therapy.
  • Tomoko Hasegawa and the team at UNC-Chapel Hill tested the efficacy of their novel immunomodulator based on HLA-G in a high-risk corneal transplant model. The results encourage further study in less immune-privileged tissues. Against control, the treated animals suffered no transplant rejection.

Advances in CRISPR Targeting

  • Profluent trained LLMs on 500m proteins and 240k type II Cas effectors to generate novel proteins with comparable on-target activity and improved specificity to SpCas9 (this can be applied to gRNAs and other proteins too)
  • Epitor Therapeutics unveiled CasNano, the smallest known CasEffector date, at just 399 AA
  • Epic Bio presented posters on small yet potent cell type specific activators that can outperform VPR
  • Many talks and posters focused on prime, RNA, and base-editing as approaches to minimize lasting off-target effects in the clinic

Thanks to the organizers, speakers, posters, and all attendees for an incredible meeting. We look forward to ASGCT2025 in New Orleans!

A large crowd of people at the ASGCT Annual Meeting, 2024, Baltimore Maryland.
Closing night party was particularly fun, with incredible food, a live band, and yes, even limbo