Antibody–Conjugated LNPs in the Spotlight: Precision Delivery for Nucleic Acid Therapeutics

Nucleic acid therapeutics are rapidly advancing, propelled into the spotlight by the success of mRNA vaccines. Modalities such as mRNA, siRNA, antisense oligonucleotides, and gene-editing technologies are showing remarkable therapeutic promise. Yet one challenge continues to define the field: how to deliver these payloads effectively.

LNPs: The Current Gold Standard

Lipid nanoparticles (LNPs) have become the leading vehicle for nucleic acid delivery. Validated at scale during the COVID-19 vaccine rollout, they are now regarded as the industry standard. Market projections reinforce this trajectory: GMI Insights estimates the global LNP market will grow from $1.1 billion in 2025 to $3.5 billion by 2034.

Despite their success, LNPs have critical limitations. Current formulations predominantly accumulate in the liver, making them highly effective for hepatic indications but far less applicable to diseases of other organs, including tumors, the lungs, the heart, and the central nervous system. Attempts to redirect LNPs often require higher dosing, which risks immunotoxicity and poor tolerability (Sharma et al. 2024). This raises a central question for the field: how do we guide LNPs to the right tissues?

Antibody-Conjugated LNPs: A Navigation System for Therapies

One of the most promising strategies is the conjugation of LNPs with antibodies—essentially giving them a built-in “navigation system” that directs delivery to specific tissues or cell types. This approach not only broadens the therapeutic reach of LNPs but also enhances safety by limiting systemic exposure and reducing immune activation.

Evidence for the power of antibody–LNPs is quickly accumulating across preclinical models. In muscle disease models, TfR1-targeted conjugates boosted drug exposure by more than 15-fold and achieved over 75% gene knockdown—an unprecedented level of precision (Malecova et al. 2023). In maternal–fetal medicine, EGFR-directed LNPs nearly doubled placental delivery, unlocking opportunities to treat conditions once considered untouchable (Geisler et al. 2024).

The momentum is equally striking in the clinic. Among the most transformative applications is in vivo CAR-T therapy, where antibody–LNPs deliver gene-modifying payloads directly into immune cells, bypassing the need for complex ex vivo engineering. AbbVie’s $2.1 billion acquisition of Capstan Therapeutics underscored this potential, bringing forward CPTX2309—a CD8-targeted antibody–LNP designed to deliver CAR mRNA into T cells—now advancing in Phase 1 trials.

Taken together, these milestones demonstrate that antibody–LNPs are no longer a distant concept, but a disruptive platform already reshaping the future of medicine.

LNP Composition and Strategies for Precision Targeting (Clemente et al. 2023)

Empowering Antibody–LNP Delivery with Diverse Modalities

LNPs are advancing beyond their role as passive carriers to become programmable platforms for precision delivery. At the same time, innovative antibody modalities—such as bispecific antibodies and nanobodies—are unlocking new opportunities to direct LNPs across multiple tissues with greater accuracy.

Biocytogen’s RenMice® platform has generated one of the world’s largest fully human antibody libraries, comprising more than one million antibody sequences. This resource spans a broad spectrum of modalities, including monoclonal antibodies, bispecific and multispecific antibodies, bispecific ADCs, heavy-chain-only antibodies (HCAbs), and TCR-mimic antibodies, creating unparalleled opportunities for the design and development of antibody–LNPs.

Recently, building on the 2022 antibody licensing agreement, Biocytogen and Merck KGaA have now expanded their collaboration to develop antibody-conjugated LNPs for nucleic acid delivery. This partnership unites Biocytogen’s antibody discovery expertise with Merck’s world-class LNP technology, driving the next wave of targeted therapeutic innovation.

Looking Ahead

LNPs are advancing at an unprecedented pace. Innovations in design—amplified by AI-driven optimization—are transforming them from simple carriers into versatile platforms capable of supporting an ever-wider range of therapeutic applications.

The field now stands at a pivotal inflection point. Precision delivery will be the key to unlocking the full promise of nucleic acid medicines, overcoming current barriers in safety, efficacy, and tissue specificity. With breakthroughs such as antibody-conjugated LNPs on the horizon, the vision of truly targeted therapies is no longer distant—it is rapidly coming into view.

FAQs: 

Q1. What is antibody–LNP delivery?

Antibody–LNP (antibody–lipid nanoparticle) delivery is a next-generation technology that attaches tissue-targeting antibodies to lipid nanoparticles. This approach directs nucleic-acid drugs such as mRNA or siRNA to specific organs or cell types, improving precision and reducing off-target side effects.

Q2. What problem does antibody–LNP technology solve?

Traditional lipid nanoparticles primarily deliver nucleic acid drugs to the liver. Antibody–LNPs incorporate targeting ligands such as bispecific antibodies, peptides, or nanobodies onto the LNP surface, guiding payloads to specific tissues like muscle, brain, or immune cells. This improves precision, safety, and therapeutic reach..

Q3. What evidence supports antibody–LNP delivery?

Preclinical studies show TfR1-targeted conjugates achieve >15-fold higher muscle exposure with strong gene-silencing effects. EGFR-targeted LNPs nearly doubled mRNA delivery to the placenta. Clinically, AbbVie’s $2.1B acquisition of Capstan Therapeutics brought a CD8-targeted Ab-LNP into Phase 1 in vivo CAR-T trials, validating this approach.

Q4. What diseases could benefit from antibody–LNP technology?

Antibody–LNPs have potential in oncology, genetic muscle diseases, neurological disorders, cardiovascular conditions, and maternal–fetal medicine. By overcoming the “liver bias” of standard LNPs, they open the door to treating tissues previously inaccessible to nucleic acid therapeutics.

Q5. What makes Biocytogen’s RenMice® platform unique for antibody–LNPs?

RenMice® models generate fully human antibodies with broad diversity. This allows pharma partners like Merck to directly screen for targeting antibodies that can be conjugated to LNPs, significantly speeding up development of precision nucleic acid medicines.

Reference:

Sharma, Preeti, et al. "The immunostimulatory nature of mRNA lipid nanoparticles." Advanced drug delivery reviews 205 (2024): 115175.

Clemente, Bruna, et al. "Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design." Frontiers in Immunology 14 (2023): 1294929.

Malecova, Barbora, et al. "Targeted tissue delivery of RNA therapeutics using antibody–oligonucleotide conjugates (AOCs)." Nucleic Acids Research 51.12 (2023): 5901-5910.

Geisler, Hannah C., et al. "EGFR-targeted ionizable lipid nanoparticles enhance in vivo mRNA delivery to the placenta." Journal of Controlled Release 371 (2024): 455-469.

Webpage:

“Lipid Nanoparticles Market Size & Share Report, 2025 – 2034.” Global Market Insights, May 2025, www.gminsights.com/industry-analysis/lipid-nanoparticles-market.

AbbVie. “AbbVie to Acquire Capstan Therapeutics, Further Strengthening Commitment to Transforming Patient Care in Immunology.” AbbVie News, 30 June 2025, news.abbvie.com/2025-06-30-AbbVie-to-Acquire-Capstan-Therapeutics,-Further-Strengthening-Commitment-to-Transforming-Patient-Care-in-Immunology.