CAPSTAN CICL-1|Ionizable Lipid for invivo CAR

Cas No.:
Chemical Name:	CICL1
Synonyms:	CICL-1,CICL 1
Purity:	>98%
Sotrage:	-20
Publication:	Hunter TL, June CH, Aghajanian H etl. In vivo CAR T cell generation to treat cancer and autoimmune disease. Science. 2025 Jun 19;388(6753):1311-1317.

Description:

CICL1 (L829) is a novel ionizable cationic lipid specifically engineered for targeted lipid nanoparticles (tLNPs) that enables efficient in vivo delivery of mRNA payloads to CD8+ T cells. Designed to overcome limitations of conventional LNPs, CICL-1 (L-829)significantly reduces off-target delivery to the liver and exhibits rapid clearance compared to benchmark lipids like ALC-0315, while demonstrating enhanced biodegradability and tolerability in rodent and primate models. When incorporated into CD8-targeted tLNPs, CICL 1 (L829 enables preferential transfection of CD8+ T cells over other immune subsets, facilitating the generation of functional anti-CD19 or anti-CD20 CAR T cells directly *in vivo*. These tLNP-engineered CAR T cells mediate rapid, deep B-cell depletion in humanized mice and cynomolgus monkeys, with repopulating B cells exhibiting a naïve phenotype suggestive of immune reset. By eliminating the need for ex vivo manufacturing or lymphodepleting chemotherapy, the L829-tLNP platform represents a safer, scalable approach for accessible CAR T therapy in oncology and autoimmune diseases.

References:

Hunter TL, June CH, Aghajanian H etl. In vivo CAR T cell generation to treat cancer and autoimmune disease. Science. 2025 Jun 19;388(6753):1311-1317.

Testing Data PDF

Cat. No.	Product name	Field of application
DC67652	CICL-242	CICL-242 is a constrained ionizable cationic lipid highlighted in patent US 20250127728A1 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.
DC67651	CICL-238	Based on the data from patent US 20250127728A1, CICL-238 emerges as a highly promising ionizable lipid candidate, demonstrating notable advantages for targeted delivery applications. It achieves exceptional transfection efficiency—reaching approximately 90% of CICL-207's performance in splenic T-cells even at a reduced lipid ratio of 50% in LNP formulations. Additionally, CICL-238 exhibits minimal off-target expression in hepatocytes (<8%, comparable to CICL-207), underscoring its enhanced specificity for immune cells over liver tissues. Its optimized structure likely contributes to efficient endosomal escape and reduced Kupffer cell uptake, making it ideal for liver-related therapies (e.g., siRNA silencing for metabolic diseases) and potentially broadening applications to genetic medicine where precision and safety are paramount. Further validation in disease models could solidify its role as a versatile, low-toxicity alternative to benchmark lipids.
DC60878	Lipid A-12	Lipid A-12 is an ionizable cationic lipid from Capstan Therapeutics and a close analog of CICL-1 (L829). The key structural distinction is in the headgroup spacer length, where the value of 'n' is 1 in A-12, compared to 0 in CICL-1 (L829).
DC67602	ILB-3132（E12LA6B603)	E12LA6B603（ILB3132，ILB-3132） is a novel ionizable amino lipid disclosed in patent WO2024198497A1, developed by MagicRNA, representing a highly efficient component for lipid nanoparticle (LNP) delivery systems.When formulated into LNPs, E12LA6B603 LNP achieves a remarkable 98.26% encapsulation efficiency for mRNA. It mediates superior in vitro transfection in dendritic cells (1.8E+05 intensity) and demonstrates best-in-class in vivo protein expression after intramuscular injection (2.2E+09 intensity). Most notably, in a B16-OVA melanoma model, therapeutic OVA-mRNA vaccines delivered by E12LA6B603 LNPs induced 100% complete tumor regression, highlighting its superior efficacy over benchmarks like DLin-MC3 and SM-102. Its biodegradable ester linkages and balanced structure make it a promising, potent candidate for next-generation mRNA vaccines and therapeutics.
DC67515	CICL-207	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.

Capstan lipid CICL-1(L829)