Compare lipid formulations with demonstrated delivery of genome-editing cargo. Study summaries identify the editing endpoint, experimental system and targeting context.
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Lipid-392 is a hydrazide-linked ionizable lipid with three tertiary amines, three palmitoyl-containing branches and a hydroxyl-bearing C10 arm. It is the carrier lipid in an optimized, cholesterol-free simplified targeted lipid nanoparticle (stLNP) containing Lipid-392, POPE and DMG-PEG2000 at 90:8.5:1.5 mol%. In mice, this formulation produced 4.93-fold greater lung luciferase expression than DOTAP-5-LNP at 0.25 mg/kg intravenous mRNA dosing, with approximately 99% of the measured lung/liver/spleen expression signal in the lung. The study also demonstrated lung-cell Cre reporter activation, adenine base editing, siRNA-mediated gene silencing and IL-10 mRNA delivery in an acute lung injury model. These preclinical results support evaluation for pulmonary RNA delivery; activity depends on formulation, payload and experimental conditions.
PA97MD101 is an ester-containing ionizable lipid with a tetraethylenepentamine-derived headgroup and two branched hydrophobic ester arms. Identified through machine-learning-guided screening and independent animal validation, its LNPs produced approximately fourfold higher hepatic luciferase expression than SM-102 in mice after intravenous Fluc mRNA delivery at 0.1 mg/kg. The study also demonstrated Cre-dependent liver recombination and Cas9/sgTtr-mediated TTR suppression. Formulation-dependent activity was associated with acidic-pH membrane activity and reduced lysosomal colocalization. PA97MD101 is a preclinical research candidate for hepatic mRNA and CRISPR cargo delivery.
LC-1 (LC-lipid-1) is an ionizable lipid identified by screening a 384-member Ugi-reaction library with a large, 5.7-kb ABE–NanoLuc mRNA cargo. The cited study evaluated LC-1 lipid nanoparticles for delivery of Cas9 and base-editing cargos to the liver, brain and lung in mice, using different formulations and administration routes.
The LUMI-6 lipid, autonomously designed via the LUMI-lab platform, is a brominated ionizable lipid optimized for mRNA delivery. Formulated at a molar ratio of 35:28:34.5:2 (LUMI-6:DOTAP:cholesterol:C14-PEG2000), LNPs exhibit uniform physicochemical properties, including a hydrodynamic diameter of ~80 nm, polydispersity index (PDI) <0.2, and robust mRNA encapsulation efficiency. In vitro, LUMI-6 LNPs demonstrated 1.8-fold higher transfection potency in human bronchial epithelial cells compared to its debrominated counterpart (LUMI-6D), with minimal cytotoxicity confirmed by CCK-8 assays. In vivo, pulmonary delivery of CRISPR-Cas9 mRNA via LUMI-6 LNPs achieved 20.3% gene editing efficiency in murine lung epithelial cells, surpassing SM-102 (Moderna’s clinical benchmark) and demonstrating preferential tropism for lung epithelium over endothelial cells—critical for inhaled therapies targeting cystic fibrosis and surfactant disorders. The brominated tail enhances endosomal escape through optimized protonation dynamics, though explicit pKa values remain unmeasured. Synthesized via high-throughput combinatorial chemistry and refined through AI-driven active learning, LUMI-6 combines scalable production with organ-selective delivery, positioning it as a transformative platform for pulmonary nucleic acid therapeutics.
11-10-8 is a degradable, branched ionizable lipidoid identified in a combinatorial screen for mRNA delivery. In the cited mouse study, its optimized LNP formulation supported liver-directed reporter mRNA expression, TTR gene editing with Cas9 mRNA and sgRNA, and FGF21 mRNA expression in a diet-induced obesity model.
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.
ALC 0307 is an ionizable amino lipid developed by Acuitas Therapeutics, serving as the critical functional component in lipid nanoparticles (LNPs) for targeted therapeutic delivery. As the core cationic lipid in specific LNP formulations (e.g., k-abe for CPS1-Q335X correction), its key feature is pH-dependent chargeability: it remains neutral at physiological pH but becomes positively charged in acidic environments like endosomes. This property enables efficient encapsulation of nucleic acid payloads (>97% efficiency, e.g., base editor mRNA/gRNA complexes) and facilitates endosomal escape via membrane disruption post-cellular uptake. Its optimized structure promotes selective hepatocyte targeting by binding endogenous apolipoprotein E (ApoE), which subsequently interacts with LDL receptors on liver cells. Preclinical studies show rapid clearance (>99.5% plasma reduction in 14 days) and manageable transient toxicity (mild, reversible cytoplasmic vacuolation in hepatocytes, short-term ALT/AST elevation). LNPs containing ALC0307, alongside helper lipids (cholesterol, DSPC, and PEG-lipid ALC-0159), form stable ~73 nm particles with low polydispersity. This combination enables repeatable, liver-directed delivery of gene editing therapeutics with minimized off-target effects, underpinning its use in individualized in vivo gene correction therapies.
ssPalmO-Phe(SS-OP) is a self-degradable material for the delivery of oligonucleotides. ssPalmO-Phe is a self-degradable derivative of ssPalm that is self-degraded in the intraparticle space by a specific hydrolytic reaction. ssPalmO-Phe is beneficial for overcoming the plasma/endosomal membrane, LNP-ssPalmO-Phe can be used to deliver both nucleic acids.
TCL053 is a three-tail ionizable lipid studied for local delivery of mRNA and separately encapsulated guide RNA to skeletal muscle in mice. The findings concern the specified research formulation and are not performance specifications for the supplied neat lipid.
CL4F8-6 is an ionizable cationic lipid (pKa = 6.14) that has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs).1 LNPs containing CL4F8-6 and encapsulating an mRNA reporter accumulate specifically in the mouse liver after intravenous administration. LNPs containing CL4F8-6 and encapsulating mRNA encoding the Cas9 nuclease (mCas9) and single-guide RNA (sgRNA) targeting Ttr (sgTtr), the gene encoding transthyretin, have been used to induce CRISPR-mediated gene knockdown in mice resulting in a reduction of serum levels of TTR.
LIPID168(pKa ~6.5) is an optimized ionizable lipid engineered for in vivo mRNA delivery to hematopoietic stem cells (HSCs) in bone marrow. Developed by Yoltech Therapeutics through high-throughput screening of lipid libraries, it features a diethylamino head group and a tailored hydrophobic tail structure that enables antibody-free targeting. When Lipid 168 was formulated into lipid nanoparticles (LNPs), it achieved 48.5% base editing efficiency in bone marrow cells —surpassing benchmarks like LIPID-028 (19.7%)—and reduced off-target liver editing from 71% to 19% by incorporating miR-122 target sequences. In humanized β-thalassemia models, LNP 168 delivered ABE8e mRNA/sgRNA to patient-derived HSCs, yielding 42.6% editing at the HBG promoter, reactivating fetal hemoglobin (γ-globin) and rescuing erythroid defects . Its bone marrow specificity is driven by a unique protein corona enriched in albumin, fibronectin, and fibrinogen . Safety studies confirmed transient immune responses and no cumulative toxicity . LIPID-168 represents a promising non-viral platform for curative gene therapies in blood disorders.
P3B is a biodegradable ionizable lipid engineered to function as a highly efficient delivery vehicle for genome-editing machinery (e.g., CRISPR-Cas9 and adenine base editors) specifically to the central nervous system (CNS). Its primary function is to encapsulate and transport large mRNA payloads across the brain-CSF interface following intrathecal administration, enabling robust and widespread gene editing in neurons and astrocytes across multiple brain regions, including the hippocampus, cortex, and thalamus. Notably, it facilitates precise single-nucleotide correction via base editing. Its targeting is intrinsically achieved by the intrathecal injection route, which localizes the nanoparticles within the cerebrospinal fluid, coupled with an optimized formulation that promotes efficient uptake and activity within CNS parenchyma while minimizing off-target exposure in peripheral organs.
RCB-4-8 is a biodegradable ionizable lipid nanoparticle (LNP) engineered for efficient pulmonary mRNA delivery and in vivo genome editing, as detailed in the primary research article "Combinatorial design of nanoparticles for pulmonary mRNA delivery and genome editing" (Li et al., Nature Biotechnology 2023）. Synthesized from a combinatorial library of 720 biodegradable lipids via a three-component reaction system, RCB-4-8 features an alkyne-containing lipid tail and tertiary amine headgroup, optimized through high-throughput screening for superior lung-targeting capabilities. Its unique molecular design incorporates hydrolyzable ester and carbonate groups, enabling rapid biodegradation (<30% lung retention at 48 h vs. >90% for conventional lipids) while maintaining high transfection efficiency. When formulated with DOTAP instead of DOPE, RCB-4-8 LNPs achieved 100-fold higher luciferase mRNA expression in murine lungs compared to FDA-approved MC3 LNPs and mediated 95% GFP knockout in vitro. In Ai9 reporter mice, intratracheal delivery of RCB-4-8 loaded with Cre mRNA edited 53% of total lung cells after three doses, while codelivery with Cas9 mRNA/sgRNA yielded 7.2% tdTomato+ cells, rising to 17% when combined with AAV-sgRNAs. With an optimal particle size of 85.7 nm (PDI 0.11) and >87% mRNA encapsulation, RCB-4-8 supports repeat dosing and represents a transformative platform for inhalable gene therapies targeting congenital lung diseases like cystic fibrosis.
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.
BiP-20 is a branched ionizable phospholipid identified as a lead compound for efficient hepatic mRNA delivery.BiP-20 is a novel, efficient, and safe liver-targeted LNP delivery vehicle. With an ideal pKa of 6.56, it achieves highly efficient liver targeting and endosomal escape primarily through the ApoE/LDL-R pathway. It demonstrates exceptional performance in gene editing at very low doses: for CRISPR-Cas9-mediated editing of TTR, a 10 μg dose achieved ~64% efficiency, which is 8-fold higher than the clinical benchmark lipid LP-01. In Prime Editing targeting the PCSK9 gene, its efficiency (4.30%) also significantly surpassed that of MC3, SM102, and LPO1. Furthermore, it mediates a 5.9-fold increase in hepatic protein expression compared to MC3. Safety assessments indicate it does not induce liver function abnormalities, showing strong therapeutic potential.
1A7B13 is a top-performing "tripod-like" lung-targeting (LuT) lipid. It forms lipid nanoparticles (LNPs) that, after intravenous injection, deliver genetic medicines (like mRNA and CRISPR-Cas9) to the lungs with over 90% selectivity, particularly favoring epithelial cells. Compared to the benchmark DOTAP LNPs, 1A7B13 LNPs achieve a 25.5-fold increase in mRNA delivery and a 9.2-fold improvement in gene-editing efficiency within the lungs. Its therapeutic potential was demonstrated by successfully delivering IL-10 mRNA to treat acute lung injury in mice.
Lipid 8 iLNPs were used to deliver CRISPR-Cas9 mRNA and sgRNA which targeted to the PLK1 gene. The safety and excellent intracerebral diffusion performance of lipid 8 iLNPs ensured that the survival of murine glioblastoma multiforme (GBM) mice was extended. The median survival was extended by approximately 50% and the overall survival was increased by 30%. The treatment of metastatic adenocarcinoma was executed by the EGFRtargeted lipid 8 iLNPs. These iLNPs possessed the ability of tumor targeting, which could increase the accumulation of CRISPR-Cas9 mRNA and sgRNA within the tumor cells. After a single intraperitoneal administration, 80% PLK1 gene was edited and the overall survival of mice with high-grade ovarian cancer malignant ascites was enhanced by 80% . These results demonstrate the clinical potential of CRISPR-Cas9 gene editing system can be delivered by iLNPs for treating tumors, and provide new ideas for tumor gene therapy.
4A3-SC7 is a proprietary, ionizable lipid component central to the SORT LNP platform developed for targeted organ delivery. It features a unique branched-tail structure designed to enhance mRNA encapsulation and endosomal escape. In the study, it served as the primary ionizable lipid in both Liver SORT LNPs and updated Lung SORT LNPs. For liver targeting, it was formulated at 15.04 mol% alongside helper lipids (DOPE: 23.04%, Cholesterol: 38.72%), PEG-lipid (DMG-PEG2000: 3.2%), and the liver-targeting lipid 4A3-Cit (20 mol%). This specific composition (Total lipid:RNA = 20:1 wt/wt) yielded LNPs with ~74 nm size, low PDI (0.17), and high encapsulation efficiency (87%) for large mRNAs like ABE editors (~5000 nt). Its branched-tail architecture was critical for stabilizing nanoparticles encapsulating large RNAs, overcoming a key limitation of previous formulations. 4A3-SC7-based Liver SORT LNPs enabled >40% base editing in hepatocytes in vivo, achieving durable correction of the disease-causing SERPINA1 mutation in PiZ mice and significantly reducing pathological protein aggregates. In the updated DualSORT system, 4A3-SC7 was also paired with DORI (instead of DOTAP) for improved lung targeting, demonstrating its versatility as a foundational ionizable lipid for multi-organ gene editing therapeutics.
306-N16B is a lipidnanoparticle, and allows systemic codelivery of Cas9 mRNA and sgRNA. 306-N16B can transport mRNA to the pulmonaryendothelial cell. 306-N16B can be used for research of genome editing-based therapies. Based on the same lipid libraries with 306-O12B, the researchers also found that N-series ionizable lipids were able to selectively deliver mRNA to the lungs of mice. Compared with the liver-targeted O-series ionizable lipids which contained ester bond in lipid tail found in previous work, such as 306-O12B, the N-series ionizable lipids with the lipid tail containing amide bond prefer to deliver mRNA to the lung. As a N-series ionizable lipid, the chemical structure of the 306-N16B is shown in Figure 4a,b. The difference of organ targeting may be due to their adsorption of different protein coronas during blood circulation caused by their different structures mentioned earlier.It has shown that the second major protein of the protein corona adsorbed by liver-targeting 306-O12B iLNPs was apolipoprotein E (ApoE), while the three dominant proteins in the protein corona adsorbed by lung-targeting 306-N16B iLNPs were serum albumin, fibrinogen beta chain, and fibrinogen gamma chain. However, the 306-N16B iLNPs showed less organ selectivity when systematically codelivered Cas9 mRNA and sgRNA in vivo, which could simultaneously activate tdTomato expression in the liver and lung of Ai14 mice, whereas single mRNA delivery could almost exclusively deliver mRNA to the lungs. This surprising phenomenon requires further investigation. Both the change of iLNPs charge and the change of lipids functional group can influence the distribution of iLNPs in vivo due to the altering of protein corona composition. Therefore, it is possible to control the organ targeting of iLNPs by controlling the composition of the outer protein corona of iLNPs.
CHCha-10 is an amino acid-derived ionizable lipid engineered for pulmonary gene therapy. Its optimal surface charge (-0.126 mV) enables efficient mucus penetration, while a pKa of ~7.0 facilitates endosomal escape. Its unique conical structure promotes membrane fusion and mRNA release. In animal models, CHCha-10-based LNPs achieved highly efficient and specific editing of lung epithelial cells, particularly stem-like basal cells (~44%), with effects persisting through tissue renewal. It also demonstrated excellent efficacy and safety in ferrets, a model closely mimicking human lung physiology.
Lipid 5D8 is a novel biodegradable ionizable lipid (IL) developed through a combinatorial chemistry strategy to overcome the limitations of conventional lipid nanoparticles (LNPs) in mRNA delivery. Synthesized via a one-step, solvent-free Michael addition reaction between amine and thiol monomers, 5D8 features asymmetric lipid tails and a biodegradable ester backbone, ensuring both structural versatility and reduced toxicity. In preclinical studies, 5D8-based LNPs demonstrated exceptional liver-targeting efficiency and mRNA delivery performance. A single intravenous dose (1 mg/kg) achieved 61% CRISPR-Cas9-mediated editing of the TTR gene in mice, reducing serum TTR protein by 90%, outperforming benchmark lipids like C12-200 (51% editing). Moreover, 5D8 enabled efficient delivery of base editors (ABE8.8 and CBE4max), achieving 42% PCSK9 editing (74% serum protein reduction) and correcting hereditary tyrosinemia in mice, significantly extending survival. Beyond gene editing, 5D8 LNPs effectively delivered siRNA (complete serum TTR clearance at 0.05 mg/kg) and enhanced hepatocyte targeting by enriching apolipoprotein E on particle surfaces. Crucially, 5D8 exhibited superior biocompatibility with no hepatotoxicity (normal ALT/AST levels), contrasting traditional LNPs. Its rapid biodegradability and "plug-and-play" design make 5D8 a versatile platform for mRNA therapeutics, holding broad potential for treating genetic disorders, cardiovascular diseases, and beyond. This innovation represents a critical advancement toward safer, high-efficiency clinical translation of gene-editing therapies.L
L31 is identified as a novel, proprietary ionizable cationic lipid that serves as the critical functional component within lipid nanoparticles (LNPs) engineered for CRISPR/Cas9 genome editing in head and neck squamous cell carcinoma (HNSCC). It was selected from a screened library of lipids for its superior performance. LNPs formulated with L31 exhibited excellent physicochemical properties, including a uniform size of 80-100 nm, low polydispersity, and high encapsulation efficiency (>85%) for both Cas9 mRNA and sgRNA. In vitro, L31-based LNPs demonstrated outstanding therapeutic efficacy, achieving approximately 68% gene editing of the oncogene SOX2 and an 88% reduction in cancer cell viability.For in vivo applications, L31-LNPs were further functionalized with anti-EGFR antibodies using the ASSET linker strategy to create targeted nanoparticles (tLNPs). This modification enhanced specific uptake by tumor cells. In a xenograft mouse model, intratumoral injection of these targeted L31-cLNPs co-encapsulating Cas9 mRNA and sgSOX2 led to potent tumor growth inhibition (90%) and a significant increase in survival, with tumor disappearance observed in half of the treated mice. In conclusion, L31 is a highly efficient ionizable lipid that forms the foundation of a potent targeted LNP platform for precise CRISPR-based cancer therapy against solid tumors.
M10 is a piperazine-derived bis-tertiary amine ionizable lipid. With an optimal pKa of 6.56, it enables efficient liver-targeted CRISPR/Cas9 delivery, achieving durable PCSK9 silencing and LDL-C reduction after a single dose, alongside a favorable safety profile.
a12Dab4 is a novel, high-performance peptide-based ionizable lipid designed specifically as the core functional building block for lipid nanoparticles (LNPs) targeting challenging or quiescent cell types, such as human hematopoietic stem and progenitor cells (HSPCs). Chemically engineered to possess a unique peptide-mimetic backbone, it provides superior membrane fusion and exceptional endosomal escape capabilities compared to older-generation, industry-standard lipids like Dlin-MC3-DMA and ALC-0315. Functionally, its primary role within the LNP formulation is to complex and efficiently encapsulate sensitive nucleic acid payloads, such as mRNA or CRISPR/Cas9 editing machinery, at an optimal nitrogen-to-phosphate (N/P) ratio. When formulated, a12Dab4 enables maximum cellular transfection and robust genome editing while exhibiting minimal cytotoxicity and preserving the long-term proliferative, self-renewing functionality of primitive stem cell compartments. Although it delivers commendable baseline transfection independently, it functions as an exceptional molecular chassis that synergies seamlessly with surface antibody conjugation (such as anti-CD34) to unlock precise, therapeutic-grade in vivo gene engineering.
E4i-200 is a branched ionizable lipid designed for efficient mRNA and CRISPR-Cas9 delivery. It features a 4-carbon (C4) lipid tail with an isopropyl (i) branch at the terminal position, enhancing its ability to disrupt endosomal membranes. The lipid is built around the 200 core, a polyamine structure (N1-(2-(4-(2-aminoethyl)piperazin-1-yl)ethyl)ethane-1,2-diamine), which facilitates mRNA encapsulation and delivery. E4i-200 excels in liver-targeted delivery, significantly improving mRNA translation and gene editing efficiency in vivo. In experiments, it outperformed linear lipids, achieving 1.5-fold higher liver luminescence compared to the gold standard C12-200. Its isopropyl branch promotes deeper membrane penetration, enhancing endosomal escape and cargo release. This lipid is particularly effective for hepatic gene editing, reducing target gene expression (e.g., TTR) by up to 90% in mouse models. Its modular design and low toxicity make it a promising candidate for mRNA-based therapies and CRISPR applications in the liver.
E8i-200 is a novel Branched Endosomal Disruptor (BEND) ionizable lipid, designed to enhance the efficiency of lipid nanoparticles (LNPs) in drug delivery, particularly for mRNA and protein delivery. Its unique structure, featuring terminal branching, improves endosomal escape, a critical step in the delivery of therapeutic cargo into cells.E8i-200 is designed to enhance endosomal escape, a key bottleneck in mRNA and protein delivery. Its terminal branching structure provides several advantages:Improved Endosomal Membrane Penetration: The branched structure allows E8i-200 to more effectively disrupt endosomal membranes, facilitating the release of mRNA and proteins into the cytoplasm.Enhanced Gene Editing Efficiency: E8i-200 has been shown to significantly improve the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes, enabling efficient gene editing in vivo.E8i-200 significantly enhanced mRNA expression in the liver, outperforming traditional linear lipids like C12-200 in mouse models.E8i-200 effectively delivered CRISPR-Cas9 RNP complexes, achieving high editing efficiency in the liver, surpassing that of linear lipids.E8i-200 also showed high transfection efficiency and low cytotoxicity in T cells, making it a promising candidate for CAR-T cell engineering and other immunotherapies.
Lipid CAD9 (3-A2-7b is a cationic degradable (CAD) lipid. 3-A2-7b formulated LNP, LNP-CAD9, can deliver FLuc mRNA to the lungs in vivo. LNP-CAD9 co-delivering Cas9 mRNA/VEGFR2 single guide RNA (sgRNA) effectively induces VEGFR2 knock out in lung endothelial cells of female mice.
CL4F11_ζ-2 is an ionizable lipid for hepatic delivery of CRISPR/Cas ribonucleoprotein (RNP). CL4F11_ζ-2 LNP shows an extremely strong inhibitory effect of serum TTR protein levels compared with all the approved ionizable lipids including DLin-MC3-DMA (MC3), SM-102, and ALC-0315.
31hP is an asymmetric A3-lipid for mRNA delivery. 31hP LNP exhibits higher stability and durability compared with MC3 LNP and SM-102 LNP. 31hP LNP achieves more efficient hepatic mRNA delivery with a much higher gene editing efficiency than MC3 LNP and LP01 LNP.
C9-200 is an ionizable cationic lipid that has been used in the formation of lipid nanoparticles (LNPs). LNPs containing C9-200 and encapsulating mRNA encoding erythropoietin (EPO) increase serum EPO levels in mice. LNPs containing C9-200 and encapsulating mRNA encoding the Cas9 nuclease and small-guide RNA (sgRNA) targeting transthyretin (TTR) induce 3-fold higher hepatic insertion and deletion (indel) formation than LNPs containing C12-200 and encapsulating mRNA encoding Cas9 in mice.
BCP-NC2-C12 is an ionizable cationic lipid designed for mRNA delivery, forming LNPs that predominantly localize to hepatic and splenic tissues in vivo. When formulated with CRISPR-Cas9 components (Cas9 mRNA and Pcsk9-targeting sgRNA), these LNPs effectively generate gene-editing indels and significantly lower circulating PCSK9 levels in murine models.
