113-AA-C8C14 is a spleen-tropic ionizable lipid with inherent splenic organ selectivity. Its formulated LNPs drastically reduce off-target liver uptake and drive 57-fold higher mRNA expression in spleen versus benchmark LNPs. It preferentially delivers nucleic acids to splenic immune cells like macrophages and T lymphocytes, supporting in vivo CAR-T engineering and mRNA vaccine research with minimal accumulation in other visceral organs.

306Oi10 is a branched ionizable lipid that can be used to construct lipid nanoparticles (LNPs) for delivering messenger RNA. The surface ionization of lipid nanoparticles is related to the effectiveness of mRNA delivery. The tail of 306Oi10 has a one-carbon branch, which provides it with stronger surface ionization compared to lipids with linear tails, thereby enhancing its mRNA delivery efficacy. 306Oi10 can be used in research related to mRNA delivery.

Lipid 11-A-M (LNP Lipid-8) is a specialized single-tail, multi-head ionizable cationic lipid engineered for targeted nucleic acid delivery to T cells. Unlike traditional lipids that exhibit strong liver tropism, 11-A-M formulations successfully bypass hepatocytes, resulting in negligible liver accumulation and toxicity. Upon intravenous administration, it naturally localizes to peripheral immune organs, enabling robust gene silencing and transfection specifically within splenic CD3⁺ T cells, with a higher efficiency in CD8⁺ cytotoxic T cells over CD4⁺ helper T cells. This liver-evading, T cell-specific targeting profile makes it a premier tool for in vivo immunotherapy and in situ cell reprogramming.

YK-009 is an advanced, biodegradable ionizable lipid designed for efficient mRNA delivery. Via intramuscular injection, it demonstrates superior targeting to draining lymph nodes, boosting immune cell transfection for vaccines. When administered intravenously, it distributes to the liver but leverages a highly degradable chemical backbone to ensure rapid clearance post-endosomal escape. This effectively eliminates the risk of long-term tissue accumulation and liver toxicity seen in traditional lipids. Delivering a balance of high transfection efficiency and exceptional biocompatibility, YK-009 is an ideal component for safe and potent lipid nanoparticle (LNP) formulations.

U-101 is an ionizable lipid for mRNA delivery. U101-LNP/IL-2F mRNA formulation demonstrats effective antitumor activity and safety.LNPs containing lipid U 101 and encapsulating mRNA encoding a fusion protein composed of IL-2, a linker, and CD25 inhibit tumor growth in an MC-38 mouse xenograft model.

6Ac1-C12 is an ester-core degradable ionizable cationic lipid developed for lung-targeted mRNA delivery. Characterized by an apparent pKa of ~6.0, it promotes efficient endosomal protonation and subsequent cargo escape. When formulated into lipid nanoparticles (LNPs) by intentionally omitting cholesterol, this lipid alters the standard in vivo distribution profile. Following intravenous injection, 6Ac1-C12 successfully shifts the primary site of mRNA accumulation and protein translation away from the liver and directly into the lungs, offering a promising, biocompatible platform for tissue-specific extrahepatic gene therapies.

IAJD93(IAJD-93) is a pentaerythritol-based one-component ionizable amphiphilic Janus Dendrimer (IAJD), delivery systems for mRNA delivery.

A10 (Compound 16) is a diketopiperazine‑based ionizable lipid disclosed in WO 2025/217298 A1 (PCT/US2025/023899) developed by NAVA Therapeutics that enables potent, cell‑selective in vivo delivery of mRNA and nucleic acids without targeting ligands. It forms stable, well‑tolerated lipid nanoparticles (LNPs) that preferentially transfect hematopoietic stem cells (HSCs), bone marrow progenitors, lung epithelium, endothelium, and immune cells while minimizing liver off‑target delivery. In both mice and non‑human primates, A10‑containing LNPs drive functional mRNA expression and gene editing in CD34⁺ HSCs at clinically relevant low doses (0.25–1.0 mg/kg), supporting in vivo HSC gene therapy without ex vivo manipulation.

KC‑34 (SPC‑A9) is a novel stereopure, diketopiperazine-based ionizable cationic lipid engineered to overcome traditional liver-restricted delivery, achieving balanced multi-organ mRNA transfection. Upon systemic intravenous administration, its precisely optimized chiral configuration allows the lipid nanoparticles (LNPs) to efficiently cross endothelial barriers and target the bone marrow, offering immense therapeutic potential for in vivo hematopoietic stem cell gene editing. Concurrently, KC-34 mediates robust and long-lasting protein expression in the spleen and lungs with minimal hepatic off-target toxicity. Its stable structure provides excellent biocompatibility and high in vivo tolerance, making it ideal for systemic, multi-dose mRNA therapies.

AKG-UO-1 is an innovative ionizable lipid engineered for targeted nucleic acid delivery, exhibiting exceptional hepatic tropism and a high affinity for metabolically active tissues. Leveraging an alpha-ketoglutarate (AKG)-inspired design, it capitalizes on the liver’s high metabolic demand to achieve precise parenchymal accumulation via systemic injection. Crucially, AKG-UO-1 selectively homing into diseased or lipid-accumulated microenvironments, where it enhances endosomal escape and mRNA translation. Its unique degradation pathway actively synergizes with host cells to alleviate metabolic stress and maintain mitochondrial homeostasis, making it an ideal candidate for treating metabolic liver diseases and fatty liver disorders.

HGT5001, disclosed in patent US 2026/0125339 A1 by Translate Bio (now part of Sanofi), is a potent ionizable cationic lipid optimized for mRNA delivery, exhibiting versatile organ tropism governed by the route of administration. When delivered via intratracheal or pulmonary administration, it effectively crosses the mucosal barrier to achieve high transfection efficiency specifically within lung tissues. Conversely, intravenous injection redirects its tropism to the liver and spleen via endogenous ApoE mediation, facilitating systemic protein replacement therapies. Engineered with an optimized headgroup, HGT5001 ensures excellent encapsulation, rapid pH-responsive endosomal escape, and superior biocompatibility with minimal systemic toxicity, making it an exceptional candidate for cystic fibrosis therapies and hepatic treatments.

Lipid 331 is a biodegradable cyclic ionizable lipid. LNPs containing Lipid 331 result in robust transfection in the nasal and lung tissues of mice and efficient transfection of lung epithelial cells and lung-resident APCs. Lipid 331 is a promising candidate for mRNA vaccine delivery, offering the potential for further enhancing the potency of mRNA vaccines.

200Oi10 is a highly potent, biodegradable ionizable lipidoid optimized for targeted mRNA delivery, with its organ tropism dynamic to the route of administration. Under intravenous injection, it demonstrates an extraordinary 97.7% liver specificity mediated by endogenous ApoE binding. Strikingly, shifting to intraperitoneal injection redirects its tropism, yielding up to 46.4% pancreatic targeting, which can be further boosted when co-formulated with DOTAP. Featuring ester-conjugated cleavable tails, 200Oi10 guarantees rapid metabolic clearance and negligible tissue accumulation toxicity, making it an exceptional candidate for localized pancreatic therapy and efficient hepatic gene delivery.

KT-001 is a novel ionizable cationic lipid developed by Vivas, Inc., disclosed in US 2026/0007612 A1 (published Jan 8, 2026).KT-001 demonstrates exceptional skeletal muscle targeting and low liver toxicity.Unlike traditional lipids that primarily accumulate in the liver, KT-001 avoids serum ApoE binding, preventing hepatic uptake. Upon intramuscular injection, it achieves a 29-fold reduction in liver off-target expression compared to standard lipids, while maintaining robust, long-lasting protein expression at the injection site.Its optimized pKa enables precise, pH-responsive endosomal escape for high transfection efficiency. KT-001 is an ideal carrier for localized mRNA vaccines and targeted therapeutics for muscle-related disorders.

93-O17O is a chalcogen-containing ionizable cationic lipidoid. It has been used in the generation of lipid nanoparticles (LNPs). LNPs containing 93-O17O localize to the spleen after intravenous injection into mice.LNPs containing 93-O17O have been used for the delivery of Cre recombinase and ribonucleoproteins for genome editing in mice and for the intratumoral delivery of cGAMP to enhance cross-presentation of tumor antigens.

CF3-2N6-UC18​​ is a rationally designed chloroquine-inspired ionizable lipid that enables robust mRNA delivery and genome editing. It integrates three modular components: a 7-trifluoromethyl-substituted quinoline scaffold (mimicking chloroquine’s endosomolytic properties), a hexamethylenediamine linker with two ionizable nitrogen atoms (pH-responsive protonation), and two unsaturated oleyl (C18:1) hydrophobic tails (enhancing membrane fusion and nanoparticle stability). This lipid self-assembles into ecoLNPs (endosomolytic chloroquine-like lipid nanoparticles) with spherical morphology (~200 nm diameter, 98% mRNA encapsulation). Its pH-sensitive activity triggers endosomal escape through dual mechanisms: ​​proton sponge effect​​ (buffering endo-lysosomal pH) and ​​saposin B-mediated membrane disruption​​ (molecular docking confirms chloroquine-like binding to lysosomal saposin B). In vitro, ecoLNPs outperform commercial reagents (18.9-fold higher mRNA delivery than Lipofectamine 2000) and penetrate 3D cell models. They resist serum/RNase degradation and retain >90% activity after 7-day storage at 4°C. In vivo, ecoLNPs achieve tissue-specific mRNA expression via multiple routes (intravenous, intramuscular, etc.), with strong lymph node tropism (90.2% after intramuscular injection) comparable to SM-102 LNPs (Moderna’s COVID-19 vaccine carrier). They mediate efficient Cre mRNA-driven recombination and CRISPR-Cas9 editing in transgenic mice. CF3-2N6-UC18’s modular design, stability, and dual endosomal escape strategies position it as a versatile platform for mRNA vaccines, gene therapy, and genome editing applications.

Lipid 87 is a proprietary ionizable lipid developed by Generation Bio. Used as a key ingredient in stealth LNPs, it greatly prolongs blood circulation time, maintains high nucleic acid encapsulation efficiency and low cytotoxicity, and enables effective liver targeting. Its relevant applications are documented in PCT patent WO2026/080826A1. As a core component (47.5–57.5 mol%) of stealth lipid nanoparticles (LNPs), it works synergistically with steric-stabilizing polymers like DSG-PEG₂₀₀₀-OMe to extend the in vivo blood half-life of LNPs to over 24 hours (compared to merely 30 minutes of conventional LNPs). It achieves an encapsulation efficiency above 95% for mRNA and closed-ended DNA (ceDNA), exhibits low cytotoxicity with an IC₅ value greater than 100 μM, and delivers robust liver-targeting performance, obtaining over 80% hepatocyte transfection at a dosage of 0.5 mpk. In preclinical models of hemophilia B, LNPs formulated with Lipid 87 can restore around 40% of clotting factor IX (FIX) activity for more than seven days.

10-Nitrooleic acid (CXA-10), a nitro fatty acid, has potential effects in disease states in which oxidative stress, inflammation, fibrosis, and/or direct tissue toxicity play significant roles.

9(10)-Nitrooleate（NOA）is an endogenous nitrated fatty acid that functions as a highly efficient bioactive molecule. Its primary role is the specific inhibition of the STING protein, a key inflammatory signaling sensor within cells. When STING is aberrantly activated, it can trigger a severe inflammatory response, leading to cellular damage.Mechanistically, NOA acts as an electrophile, capable of covalently modifying specific cysteine residues on the STING protein, thereby effectively blocking its ability to activate downstream signaling pathways. This inhibitory action establishes NOA as a potent endogenous anti-inflammatory agent. In practical application, loading NOA into delivery systems, such as lipid nanoparticles, equips them with an intrinsic "molecular fire extinguisher." It significantly mitigates the acute inflammatory response triggered by delivered cargo, effectively transforming otherwise toxic delivery vehicles into safe platforms. The core value of NOA lies in its ability to provide exceptional safety without compromising the functional expression of therapeutic payloads, offering a crucial safeguard for achieving long-term treatments.

6A1‑SC8 is a biodegradable ionizable lipid developed for LNP-based nucleic acid delivery. With multi-tertiary amine core enabling optimal endosomal escape and built-in hydrolyzable ester linkages for in vivo metabolic clearance, it efficiently encapsulates mRNA, sgRNA and gene-editing payloads. When blended with helper lipids or modified via the SORT strategy with cationic additives like DOTAP, it generates organ-targeted LNPs ranging from liver to cardiac tropism, widely applied in preclinical gene therapy, in vivo CAR‑T and rare disease therapeutic research.

AO12 is a novel antioxidant ionizable lipid derived from SM-102 skeleton with para-hydroxyphenyl propionic acid side chains. Integrated into LNPs, it efficiently scavenges diverse reactive oxygen species including ·OH and ONOO⁻, shielding encapsulated mRNA from oxidative degradation. It retains fine LNP formulation features and cellular uptake capacity of conventional lipids, boosting in vivo mRNA translation. Applied for regenerative mRNA therapy and CRISPR gene editing against fibrosis and inflammatory disorders.

YHS-12 is an ionizable cationic lipid (pKa = 6.506) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA and mRNA in vitro and in vivo.1 LNPs containing YHS-12 and the macrophage targeting peptide CRVLRSGSC and encapsulating mRNA encoding chimeric antigen receptor targeting methicillin-resistant S. aureus (MRSA) and siRNA targeting caspase-11 increase the phagocytosis rate of MRSA in RAW 264.7 macrophages and primary mouse bone marrow-derived macrophages (BMDMs). Intravenous administration of these LNPs decreases blood bacterial burden and increases survival in a model of sepsis using cyclophosphamide-induced immunosuppressed mice.

A33-D268 is an ionizable lipid derived from a 2-aminoimidazole (AM) core, featuring an asymmetric hydrophobic tail structure designed to optimize mRNA interactions. Selected as the top candidate from a 21-lipid library through molecular dynamics (MD) simulations, it demonstrated superior performance: low root mean square deviation (RMSD) and the smallest radius of gyration (Rg), indicating tight mRNA compaction, alongside moderate electrostatic energy and above-average hydrogen bonding for stable encapsulation. Formulated into LNPs, it achieves ​​efficient muscle-specific transfection​​ post-intramuscular injection, rivaling commercial ALC-0315 LNPs. Crucially, it exhibits ​​29-fold lower hepatic off-target expression​​, attributed to its inability to leverage serum protein coronas for liver tropism.

4A2-B8-PH is an optimally designed thioketal-incorporated biodegradable ionizable lipid (TBIL) for mRNA delivery to pancreatic ductal epithelial cells. It features a 4A2 headgroup with three tertiary amines, a biodegradable thioketal-based B8 linker, and a branched PH tail. The thioketal linker enables ROS-responsive degradation in the tumor microenvironment, enhancing endosomal escape and mRNA release. In vivo, 4A2-B8-PH LNPs achieve 98.3% pancreas-specific targeting after intraperitoneal administration, with a 218-fold improvement in delivery efficiency compared to previous benchmarks. It successfully transfects 30.5% of pancreatic ductal epithelial cells and induces complete tumor regression in orthotopic PDAC models via IL-12 mRNA therapy, demonstrating high efficacy and safety.

​​C-a16​​ is an ionizable lipid engineered through Mannich reaction chemistry, designed to revolutionize mRNA delivery by synergizing high efficiency with minimized immune activation. Synthesized by reacting a phenolic tail derivative, formaldehyde, and a branched tertiary amine core under optimized ethanol conditions, this lipid integrates antioxidant phenol groups directly into its structure. These phenol moieties serve as intrinsic radical scavengers, effectively neutralizing intracellular reactive oxygen species that typically degrade mRNA and trigger inflammation.In lipid nanoparticle formulations, C-a16 constitutes the functional backbone, enabling superior mRNA encapsulation efficiency while maintaining a stable nanoparticle size of approximately 80–100 nm. Critically, it outperforms conventional lipids like DLin-MC3-DMA by achieving significantly higher target-protein expression in vivo alongside markedly reduced pro-inflammatory cytokine secretion. The antioxidant capability is not incidental but fundamental—quenching the phenol groups drastically diminishes both ROS suppression and delivery efficacy, confirming the design's mechanistic elegance.C-a16 represents a paradigm shift: its biomimetic antioxidant architecture addresses the chronic trade-off between delivery potency and immunogenicity, unlocking safer therapeutic applications for vaccines and gene therapies.

C14-490 is an ionizable cationic lipid (pKa = 5.94).1 It has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA in vivo.C14-490-containing LNPs accumulate primarily in the fetal mouse liver and, to a lesser extent, in the lungs, intestine, and brain after vitelline vein injection on gestational day 16 (E16).1 CD45-functionalized LNPs containing C14-490 and encapsulating mRNA encoding GFP transfect Jurkat cells, which constitutively express the CD45 receptor (CD45R).C14-490-containing CD45-functionalized LNPs encapsulating Cre mRNA mediate genome modulation in bone marrow hematopoietic stem cells (HSCs) for at least four months after in utero injection in R26mT/mG mice at E13.5.

CICL-242​ is a constrained ionizable cationic lipid highlighted in patent US 20250127728A1 developed by Capstan as a promising candidate for advanced therapeutic delivery, particularly in stem cell and gene editing applications. Its structure features a rigid amine headgroup similar to CICL-207, which likely facilitates efficient endosomal escape and reduces non-specific uptake, enhancing targeted nucleic acid delivery. Although detailed performance data is not fully disclosed in the patent, CICL-242 is explicitly synthesized and included in gene editing experimental systems (e.g., CRISPR-Cas9 workflows), suggesting its potential for high-efficiency transfection in hard-to-transfect cells​ like hematopoietic stem cells (CD34⁺). This makes it a strong candidate for ex vivo cell engineering and regenerative medicine, where precision and low off-target effects are critical. While further validation is needed to quantify its efficacy and safety profile, CICL-242 represents a strategic innovation in the lipid library for next-generation genetic therapies.

CICL 207 is structurally optimized based on Lipid CICL-1. CICL207​​ is a constrained ionizable cationic lipid designed for lipid nanoparticle (LNP) delivery systems developed by Capstan. Its structure features a ​​rigid cyclic backbone​​ (e.g., pyrrolidine-derived core) paired with a ​​tertiary amine group​​ that ionizes at acidic pH (pKa ~6.5–7.0), enhancing endosomal escape. The lipid includes ​​asymmetric hydrophobic tails​​ (likely C14–C18 alkyl/ester chains) to stabilize LNP membranes and improve nucleic acid encapsulation. Integrated into LNPs (e.g., 58% CICL-207, 10% DSPC, 30.5% cholesterol, PEG-lipids), it enables targeted delivery to T cells (anti-CD5/CD8 tLNPs) with ​​high transfection efficiency​​ (spleen T cells >70% mCherry+), ​​reduced liver uptake​​, and ​​low toxicity​​ (no significant ALT/AST elevation in rats). Its constrained design balances stability, tissue specificity, and biocompatibility for gene therapy applications.CICL 207 (F50) significantly outperforms CICL-1 by delivering dramatically enhanced target cell transfection with reduced off-target effects. It achieves >50% transfection efficiency in splenic T-cells—nearly double that of CICL-1—while slashing off-target expression in liver cells to <5% (versus >15% for CICL-1. This precision translates to superior therapeutic outcomes: CICL-207 enables ~95% B-cell depletion in CAR-T applications, far exceeding CICL-1 ’s ~60% efficacy. Critically, it maintains an exceptional safety profile, showing no significant liver toxicity or inflammatory cytokine elevation even at high doses. Furthermore, CICL-207 demonstrates 2-fold higher transfection efficiency in hematopoietic stem cells, enabling robust gene editing. Its optimized pKa (~6.5) and constrained amine structure enhance endosomal escape while minimizing Kupffer cell uptake, making it ideal for targeted therapeutics requiring both potency and safety.​

VL-422 is an ionizable cationic lipid. VL-422 delivers CRISPR complementary single-guide RNA (sgRNA) and Cas9 mRNA to enable in vitro and in vivo gene editing. LNPs containing VL-422 loaded with Cas9 mRNA and sgRNA targeting the ANGPTL3 gene induce the deletion of premature stop codons within the ANGPTL3 gene in the liver of cynomolgus monkeys. Loss-of-function of ANGPTL3 leads to decreased levels of LDL, HDL and cholesterol in plasma. The VL-422 delivery system can be used for the research of gene editing strategies targeting lipid metabolism diseases.

Lipid 11 is the optimal ionizable lipid disclosed by Liberate Bio, Inc. in patent WO2025/250730 A1, which can significantly improve the delivery efficiency of nucleic acid drugs to extrahepatic tissues including bone marrow, spleen and muscle, with excellent in vivo stability and safety.