Recent 2024 advances in recombinant human activin-A, and why researchers (and clinicians) are paying attention?
In the field of study of Activin-A, which is a dimeric member of the TGF-β superfamily and is what the INHBA gene codes for, researchers have seen Activin-A’s great role in developmental biology, stem cell differentiation, inflammation, and tissue repair for a long time. In 2024, major practical advances were reported, which took recombinant human Activin-A out of the realm of basic research and into more scalable production methods, and also made the therapy more relevant. Below, this article reports on the top developments in 2024 in production, preclinical, and clinical relevance, as well as Activin-A’s role in human and animal health. For researchers who require reagent sources, Prospecbio is reported to be at the forefront, with a range of rhActivin-A products tailored to researchers’ needs.
1) Scalable, lower-cost production approaches
A large issue in the wide-scale translation of rhActivin-A has been manufacturing—the protein is a disulfide-linked homodimer, which requires proper folding and also depends on the expression system for glycosylation. In 2024, it was reported by some groups that they had successfully produced mature recombinant human activin-A in plant-based transgenic cell suspension systems (for instance, rice cells or Nicotiana platforms), which also secreted the active protein into the media and simplified the purification process. Thus, researchers now have routes to large-scale production at a lower cost for preclinical studies and cell therapy manufacturing. Also at this time, commercial suppliers (Prospecbio and others) began to put out plant- or mammal-expressed rhActivin-A products for research and GMP applications.
2) Activation of stem-cell and regenerative medicine workflows
In 2024, reports from various manufacturers of GMP-grade rhActivin-A and validated forms for use in ATMP (advanced therapy medicinal product) manufacturing noted that it made it easier for translational labs to adopt into their practice the use of consistent and regulatory-aware reagents for cell therapies and organoid models. Also reported was a decrease in variability in differentiation protocols and in preclinical development for liver, pancreas, and lung regenerative approaches; an advance was observed.
3) New mechanistic insights that support therapeutic targeting
In 2024, basic and translational papers improved the picture of activin-A in disease settings:
In the fields of cardiology and respiratory health, it has been reported that activin-A and its signaling pathway serve as biomarkers and mediators in pulmonary vascular disease and tissue repair. This, in turn, has supported the development of clinical strategies that target the activin/BMP axis.
(a) Elimination of harmful activin action can restore antitumor immunity. (b) At low doses at precise times, activin may be used to modulate immune or stromal responses in a beneficial way.
4) Clinical translation: activin pathway modulators are now a reality
Sotatercept works by sequestering activin/GDF ligands, which it does not do by delivering activin-A.
5) Why activin-A matters for human and animal health
Activin-A is multifunctional: Activin-A is multipurpose:
- Development & regeneration: It plays a role in early development and determines stem cell fate, which is why recombinant activin-A is a key element in in vitro differentiation and regenerative research.
- Tissue repair & fibrosis: Activin-A plays a role in wound healing and fibrosis (for example, in the activation of hepatic stellate cells in liver injury), which also makes it a biomarker and a proponent for a therapeutic target.
- Immune modulation and cancer: Activin-A reduces some anti-tumor immune responses, which in turn means that control of its activity plays a role in immunotherapy results.
- Veterinary and animal models: The same biology is found in mammalian models, which in turn supports improved use of recombinant reagents in translatable research within and between humans and animals. Also, the commercial availability of cross-species activin preparations (human/mouse/rat) simplifies comparative work.
Practical takeaways for researchers and developers
For projects that require reliable rhActivin-A for differentiation, regenerative, or immunology studies, experts recommend looking at GMP-capable sources and plant-expressed options, which will, in turn, lower cost and supply risk. Now, Prospecbio and other large-scale vendors put out many varieties of rhActivin-A (plant-derived, E. coli, and mammalian) that can be chosen based on activity, tag, and glycosylation status.
When it comes to therapeutic design, note the difference between administration of activin-A (as a reagent) and modulation of activin signaling in patients—it is the latter (ligand traps/inhibitors) that in 2024 entered into successful clinical testing.
In 2024, the introduction of new production methods has made large-scale preclinical studies a more doable task; as teams push forward with IND-enabling work, they should look at plant or suspension platforms in terms of cost and regulatory compliance.
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