The approval of the first CRISPR-based therapy in late 2023—CRISPR Therapeutics and Vertex Pharmaceuticals’ Casgevy (exagamglogene autotemcel or exa-cel) for sickle cell disease and β-thalassemia—was a landmark for the field of genome editing. A year on though, very few patients have yet received the therapy, in part because of its complex delivery requirements, which include the collection of hematopoietic stem and progenitor cells (HSPCs), ex vivo modification and aggressive chemotherapy before the cells are transplanted back.

The ability to make genome modifications in vivo rather than ex vivo could be the key to realizing the potential of therapies like Casgevy, as well as many others. This goal is the focus of one of three recent major drug delivery deals, selected with the help of data from DealForma. In January 2025, Vertex partnered with Orna Therapeutics to use Orna’s lipid nanoparticle (LNP) technology, which has been reported to enable the delivery of messenger RNA (mRNA) to HSPCs in preclinical models, to develop in vivo gene-editing therapies for sickle cell disease and transfusion dependent β-thalassemia (TDT) (see Deal snapshot).

Adeno-associated virus (AAV) vectors are also being explored for the delivery of gene therapies. In December 2024, Sangamo Therapeutics signed a licensing agreement allowing Astellas to use Sangamo’s neurotropic AAV capsid, known as STAC-BBB, to deliver genomic medicines for neurological disease targets (see Deal snapshot). This was Sangamo’s second major deal in 2024 around STAC-BBB, which has been reported to achieve penetration of the blood–brain barrier (BBB) after intravenous administration. In August, Sangamo signed a deal with a headline value of $1.95 billion with Genentech to develop intravenously administered medicines for neurodegenerative diseases using STAC-BBB, as well as Sangamo’s zinc finger technology to target tau.

Technology to cross the BBB was also a key part of AbbVie’s acquisition of Aliada Therapeutics for $1.4 billion in the fourth quarter of 2024 (see Deal snapshot). In this case, Aliada’s platform exploits receptors that are expressed on brain endothelial cells to enable uptake of biologic modalities including antibodies and oligonucleotides, such as its lead candidate for Alzheimer’s disease, an antibody targeted at a form of amyloid-β.

Vertex Pharmaceuticals partners with Orna on LNPs to deliver gene editing therapies

Deal announced: 7 January 2025

Potential deal value: $4.08 billion

Deal overview:

• Orna Therapeutics, a biotech founded in Massachusetts in 2019, will work with Vertex Pharmaceuticals to use Orna’s lipid nanoparticle (LNP) technology to develop next-generation in vivo gene editing therapies for sickle cell disease and transfusion dependent β-thalassemia (TDT).

• Orna, which was founded around circular RNA technology, gained the LNP technology for the delivery of RNA-based therapies to tissues beyond the liver, including hematopoietic stem cells, through its acquisition of ReNAgade Therapeutics in May 2024.

• Under the terms of the deal, Orna received $65 million upfront, and could receive up to $635 million in milestone payments related to products for sickle cell disease and TDT. Orna is also eligible to receive up to $365 million per product in option fees and milestone payments for up to ten products if Vertex exercises its option rights for additional indications.

Sangamo Therapeutics grants license for neurotropic AAV capsid to Astellas

Deal announced: 19 December 2024

Potential deal value: $1.32 billion

Deal overview:

• Sangamo Therapeutics entered a license agreement with Astellas to use Sangamo’s proprietary adeno-associated virus (AAV) capsid to deliver genomic medicines for up to five targets for neurological diseases.

• Sangamo’s neurotropic AAV capsid, known as STAC-BBB, has been reported to enable robust penetration of the blood–brain barrier (BBB) and widespread transgene expression in the brain of non-human primates after intravenous administration.

• Under the terms of the agreement, Sangamo received $20 million upfront, and Astellas gained an exclusive global license to use the STAC-BBB capsid for one target, with the right to add up to four additional targets after paying further license fees. Overall, Sangamo is eligible to receive up to $1.3 billion in target licensing fees and milestone payments across all five potential targets, as well as sales royalties for resultant products.

AbbVie gains CNS delivery platform through Aliada Therapeutics acquisition

Deal announced: 28 October 2024

Potential deal value: $1.4 billion

Deal overview:

• AbbVie acquired Aliada Therapeutics, a Boston-based biotech company developing therapies for central nervous system (CNS) diseases using a modular technology platform known as MODEL to deliver them across the BBB.

• The MODEL platform was originally designed by researchers at Janssen. It uses engineered protein domains that bind to either the transferrin receptor or CD98, which are highly expressed on brain endothelial cells, to mediate the cellular uptake of attached biologic modalities including antibodies and oligonucleotides through receptor-mediated transcytosis.

• Aliada’s lead candidate, ALIA-1758 for the treatment of Alzheimer’s disease, harnesses the transferrin receptor to transport an antibody targeted at pyroglutamate amyloid-β across the BBB. It is currently in a phase 1 trial.

• AbbVie agreed to pay $1.4 billion in cash for the acquisition of Aliada Therapeutics, which was completed in December 2024.