Compare RNA delivery to primary T cells in vivo and ex vivo. Each study identifies the lipid, formulation context, cell population and delivery setting.
Ionizable lipids are central components of many lipid nanoparticle systems for nucleic-acid delivery. During formulation they contribute to cargo association and particle assembly. Lipids designed to remain comparatively neutral near physiological pH can become protonated under acidic endosomal conditions, which may support membrane interaction and cytosolic cargo release.
DC Chemicals provides research-use lipids for candidate screening, formulation development and mechanistic studies. Our capabilities include complex lipid synthesis, purification, analytical release and process-development support; product-specific commercial specifications remain separate from any literature-reported formulation or biological performance.
DC Chemicals has independently developed ionizable-lipid structures supported by company-owned intellectual property, and selected proprietary lipid programs have advanced to GMP-stage development.
We welcome joint development with customers—from molecular design and lipid synthesis through route and process development. We can also support custom synthesis of GMP-grade ionizable lipids to agreed technical specifications and quality requirements.
Discuss a co-development project →Lipid 6 is a literature-reported ionizable lipid for ex vivo mRNA delivery to primary human T cells. In Gao et al. (2026), LNPs containing Lipid 6 generated MUC1-CAR T cells that were assessed against MUC1-positive cancer cell lines in vitro.
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.
PL-40 is a cardiolipin-mimetic ionizable lipid engineered for high-efficiency, antibody-free mRNA delivery to T cells. PL 40 LNPs exhibit a mean particle size of 120 nm, zeta potential of -5.19 mV, and >80% mRNA encapsulation efficiency, with excellent plasma stability (≤5% size change after 6h in serum). Cryo-TEM reveals polyhedral nanoparticles with phase-separated domains, while SAXS confirms tight mRNA packing (d-spacing: ~3 nm vs. 6.64 nm in conventional LNPs). AFM demonstrates exceptional rigidity (high bending modulus), enabling T cell-selective uptake via actin-mediated endocytosis (>2× higher than ALC0315 LNPs).In primary human T cells, PL40 LNPs achieve >90% transfection at 0.5 μg mRNA dose and sustain >100× higher luciferase expression than benchmark lipids. When delivering circular RNA, they extend protein expression >5 days with superior spleen tropism (spleen:liver ratio = 2.63). Crucially, they reprogram T cells into functional CAR-Ts in vivo without antibody conjugation, evading exhaustion markers (no Tim-3/PD-1 upregulation). Therapeutically, PL40-based uPAR-targeted CAR mRNA reduces liver fibrosis (collagen↓50%, ALT↓50%) and rheumatoid arthritis severity (clinical scores↓60%) by clearing senescent cells. Humanized anti-uPAR CARs delivered via PL40 show near-complete cytotoxicity (>95%) against uPAR+ cells, underscoring clinical translatability.
Lipid 15 is the lead ionizable cationic lipid (ICL) for CD8-targeted mRNA-LNPs. As the core LNP component, Lipid 15 yields ~100 nm uniform particles with near-neutral surface charge at physiological pH, while becoming strongly cationic in acidic endosomes—reducing hepatic off-target uptake and enabling efficient endosomal escape to release mRNA. Versus other ICL candidates, Lipid 15 achieves far higher mRNA transfection efficiency in primary human CD8⁺ T cells, supports robust transient CAR expression, and triggers minimal cytokine release in immunogenicity assays. It retains structural and functional stability after freeze storage. When formulated into anti-CD8 VHH-conjugated LNPs carrying CD22 CAR mRNA, Lipid 15 drives specific in vivo reprogramming of circulating CD8⁺ T cells into functional CAR-T cells, delivering potent tumor suppression in humanized hematological malignancy models without overt toxicity.
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.
93-O17S is an imidazole-based synthetic lipidoid for in vivo mRNA delivery. Lipid nanoparticles (LNPs) with 93-O17S promotes both the cross-presentation of tumor antigens and the intracellular delivery of cGAMP (STING agonist).
C12-200 is a well-known cationic lipid used in the formulation of lipid nanoparticles (LNPs) for the delivery of therapeutic nucleic acids, including siRNA, mRNA, and CRISPR components. It is widely recognized for its high in vivo potency at low doses and is often used as a positive control ionizable lipid in research exploring new ionizable lipids.
C14-4 (C14-494,Lipid B-4,Lipid B4) is a novel ionizable lipid with the highest T-cell transfection efficiency and low cytotoxicity.The C14-4 ionizable lipid has been explored for CAR-T therapy.To screen the excellent formulations for mRNA delivery, a lipid library of 24 ionizable lipids was constructed to make iLNPs, which were used to deliver luciferase mRNA into Jurkat cells.[115] The optimal iLNPs formulation was C14-4 iLNPs (C14-4 ionizable lipid, DOPE, chol, and PEG at a molar ratio of 35%, 16%, 46.5%, and 2.5%) (Figure 6c). The optimal dose of luciferase mRNA for C14-4 iLNPs was 30 ng. Compared with electroporated CAR T cells, the CAR T cells engineered via C14-4 iLNPs showed potent cancer-killing activity when they were cocultured with Nalm-6 acute lymphoblastic leukemia cells. To obtain a safer and more effective CAR mRNA delivery vehicle, the orthogonal design provided 256 potential formulations, and 16 representative iLNPs formulations were evaluated.Through evaluating the safety, delivery efficiency, and transfection efficiency of 16 iLNPs, the formulation B10 (C14-4 ionizable lipid, DOPE, chol, PEG at a molar ratio of 40%, 30%, 25%, and 2.5%) was screened out as the optimal performing formulation. The luciferase expression based on B10 formulation was increased threefold than the initial formulation. Reducing the accumulation and clearance of iLNPs in the liver can increase the expression of CAR mRNA in T cells, further improving the therapeutic effect of CAR-T. Studies have shown that cholesterol analogs can alter the mechanisms of intracellular circulation and enhance the delivery of mRNA, which may be related to the reduced recognition of iLNPs by the Niemann Pick C1 (NPC1) enzyme.The addition of a hydroxyl group to various locations in the cholesterol molecule can alter the binding kinetics between the modified cholesterol and NPC1, and reduced NPC1 recognition of cholesterol. The results showed that replacement of 25% and 50% 7 α-hydroxycholesterol for cholesterol in iLNPs improved mRNA delivery to primary human T cells in vitro by 1.8-fold and twofold, respectively.C14-4 is one of the ionizable lipids to efficiently deliver mRNA to Jurkat cells or primary human T cells. It will effectively promote the development of mRNA delivery by iLNPs for CAR-T therapy.
76-O17Se is a selenium-containing lipidoid investigated for intracellular delivery of mRNA and genome-editing proteins. In CAR-T cell engineering studies, 76-O17Se-based lipid nanoparticles delivered N1-methylpseudouridine-modified anti-CD19 CAR mRNA into CD8+ T lymphocytes. The resulting CAR-T cells demonstrated cytotoxic activity against B-cell lymphoma cells in vitro, supporting its application in nonviral mRNA delivery and transient immune-cell engineering research.
Lipid C14-A1 is an ionizable lipid. C14-A1-LPN is a potent and safe LNP platform to deliver Foxp3 mRNA to CD4+ T cells to engineer immunosuppressive FP3T cells.
Lipid C12-A1 is an ionizable lipid. C12-A1-LPN is a potent and safe LNP platform to deliver Foxp3 mRNA to CD4+ T cells to engineer immunosuppressive FP3T cells. C12-A1 has a slightly lower average cell viability than C14-A1.
H5T5 is a leading ionizable lipid nanoparticle (LNP) formulation optimized for in vivomRNA delivery, featuring a pKa of 6.51, a size of ~154 nm, and a narrow polydispersity index (PDI) of 0.05. It demonstrated superior in vitromRNA transfection efficiency in primary immune cells, such as bone marrow-derived macrophages. Following intravenous administration, H5T5 exhibits precise organotropism, predominantly targeting the spleen and bone marrow, where it effectively delivers mRNA to a broad spectrum of immune cells, including macrophages, dendritic cells, T cells, B cells, and NK cells. This capability enables its core application: the in vivogeneration of "pan-CAR" immune cells. When loaded with anti-HER2 CAR mRNA, the H5T5-based therapy achieved potent tumor regression and prolonged survival in multiple solid tumor models. Preliminary safety assessments indicated a manageable cytokine profile and no significant organ toxicity, positioning it as a promising platform for in vivocell engineering.
Trp-L1-T4 is a novel tryptophan-derived ionizable lipid that serves as the core functional component of the optimized lipid nanoparticle (TLNP/RLNP) platform. Its primary function is to enable the efficient encapsulation and in vivo delivery of self-amplifying RNA (saRNA) cargo. Specifically, it facilitates high transfection efficiency and cytosolic release of the RNA payload in target follicular helper T (Tfh) cells, with minimal cytotoxicity. This capability is crucial for reprogramming pathogenic Tfh cells into regulatory CAR-Tfh cells, forming the foundation of the study's therapeutic strategy.
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.
Lipid 10a-26 is an ionizable lipid developed by Orna Therapeutics for lipid nanoparticle (LNP) formulations. Lipid 10a-26 is a key ionizable lipid in the LNP-6 formulation. Through structural modification, it exhibits reduced binding to ApoE proteins and lowered liver affinity compared to traditional ionizable lipids. Instead, Lipid 10a-26 demonstrates strong splenic tropism—in non-human primate studies, it effectively delivers payloads to the spleen and immune cells in peripheral blood, such as T cells, NK cells, and macrophages, enabling the possibility of "in vivo CAR-T" therapy. Its pKa is tuned to approximately 6.0–6.5, allowing rapid protonation in the acidic endosomal environment, which promotes endosomal membrane disruption and efficient cytosolic release of circular RNA.
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.
E10i-494 is a branched ionizable lipid designed to enhance the delivery of mRNA and CRISPR-Cas9 ribonucleoprotein (RNP) complexes. It belongs to the Branched Endosomal Disruptor (BEND) lipid family, which features terminal branching to improve endosomal escape and cellular uptake.E10i-494 demonstrated exceptional performance in T cell engineering, achieving >80% transfection efficiency in primary human T cells. This is significantly higher than the ~70% efficiency achieved by the linear lipid C14-494.The isopropyl branch enhances the lipid's ability to penetrate and disrupt endosomal membranes, leading to improved release of mRNA and RNPs into the cytoplasm.Despite its high efficiency, E10i-494 exhibits low cytotoxicity, making it suitable for therapeutic applications.E10i-494 is particularly effective for delivering mRNA to T cells, making it a promising tool for CAR-T cell therapy and other immunotherapies.Its ability to deliver CRISPR-Cas9 RNPs efficiently also makes it suitable for in vivo gene editing applications.
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.
TE-EP8-S is a single-component, ionizable cationic lipid designed specifically for the targeted delivery of mRNA to T cells within the spleen. This innovative lipid formulation enhances the efficiency and precision of mRNA-based therapies by ensuring optimal cellular uptake and expression in immune cells. Its unique structure and properties make it a promising tool for advancing immunotherapeutic applications.
1-A-N is a lipid nanoparticle (LNP) used for in vivo delivery of siRNA. 1-A-N can regulate immune response by delivering siCD45 (siRNA targeting CD45) to T cells and silencing the CD45 gene.
Lipid 6 is the lead ionizable lipid among eight candidates screened by Gao et al. for mRNA delivery to primary human immune cells. Lipid 6 LNPs were used to generate MUC1-CAR T cells ex vivo and to assess their cytotoxicity against MUC1-positive cancer cell lines in vitro. Mouse reporter-mRNA expression was studied separately; in vivo antitumor efficacy of the CAR T cells was not established.
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, L829 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, 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.
| Lipid | Delivery setting & functional evidence | Source & study details |
|---|---|---|
| Ex vivo primary T-cell delivery | ||
| Lipid 6 (Gao et al., 2026) DCL0005 | Ex vivo primary human T-cell transfection Ex vivo mRNA delivery to primary human T cells; MUC1-CAR expression and antigen-dependent cytotoxicity were measured in vitro. Mouse reporter delivery is a separate experiment. | [1] Source Figs. 3–6; SI Table S2 |
| C12-200 DC58046 | Ex vivo activated primary human CD4+ T-cell transfection C12-200 LNPs were a reporter-mRNA transfection benchmark in activated primary human CD4+ T cells ex vivo. This does not assign the study's C14-A1 Foxp3 engineering results to C12-200. | [2] Source Fig. 2B–D; SI Fig. S1; Results, primary human CD4+ T-cell screen |
| C14-4 DC59010 | Ex vivo primary human T-cell transfection C14-4 LNPs delivered anti-CD19 CAR mRNA to primary human T cells ex vivo; the engineered cells killed target leukemia cells in vitro. Crude and purified lipid formulations were compared separately. | [3] Source Figs. 4–6; primary human T-cell transfection and cytotoxicity assays |
| 76-O17Se DC60494 | Ex vivo primary human CD8+ T-cell transfection 76-O17Se delivered anti-CD19 CAR-eGFP mRNA to primary human CD8+ T cells ex vivo. Expression and cell viability must be interpreted together. | [4] Source SI Figs. S5A–C and S6 |
| C14-A1 DC60499 | Ex vivo primary human CD4+ T-cell transfection C14-A1 LNPs delivered Foxp3 mRNA to primary human CD4+ T cells ex vivo and generated transient immunosuppressive FP3T cells. | [2] Source Figs. 2–4 |
| C12-A1 DC60503 | Ex vivo primary human CD4+ T-cell transfection C12-A1 LNPs supported reporter mRNA expression in primary human CD4+ T cells ex vivo. The downstream Foxp3 engineering experiments used C14-A1, not C12-A1. | [2] Source Fig. 2B–D; SI Fig. S1 |
| 93-O17O DC82105 | Ex vivo primary T-cell transfection 93-O17O supported reporter mRNA expression in the ex vivo primary T-cell screen. In vivo results for 93-O17S must not be assigned to this oxygen-tail analogue. | [5] Source Fig. 3C, initial primary-T-cell screen |
| E10i-494 DC13101 | Ex vivo activated primary human T-cell transfection E10i-494 BEND LNPs delivered reporter mRNA to activated primary human T cells ex vivo. The study's hepatic gene-editing results belong to different lipid/formulation experiments. | [6] Source Fig. 7 |
| Lipid 6 DC68234 | Ex vivo primary human T-cell transfection Ex vivo mRNA delivery to primary human T cells; MUC1-CAR expression and antigen-dependent cytotoxicity were measured in vitro. Mouse reporter delivery is a separate experiment. | [1] Source Figs. 3–6; SI Table S2 |
| In vivo primary T-cell delivery | ||
| CICL-207 DC67515 | Intravenous CICL-207 LNPs conjugated to anti-CD5 antibody delivered mCherry mRNA to splenic T cells after intravenous administration in mice. Targeting depends on the antibody-functionalized formulation. | [7] Source Example 66, Fig. 1A; anti-CD5 tLNP, mouse tail-vein dose, splenic T-cell mCherry expression |
| CICL-1 (L829) DC99010 | Intravenous CICL-1/L829 LNPs conjugated to anti-CD5 antibody delivered mCherry mRNA to splenic T cells after intravenous administration in mice. Targeting depends on the antibody-functionalized formulation. | [7] Source Example 66, Fig. 1A; anti-CD5 tLNP, mouse tail-vein dose, splenic T-cell mCherry expression |
| Lipid H5T5 DC60925 | Intravenous Mouse IV study: H5T5 LNPs supported splenic reporter expression and CAR expression across several splenic immune-cell populations. | [8] Source Figure 3A–F |
| Lipid 10a-26 DC82209 | Intravenous Lipid 26 LNPs supported Cre circular-RNA expression in splenic T-cell populations in Ai9 mice; this is broader immune-cell delivery rather than T-cell-exclusive targeting. | [9] Source Paragraphs [0861]–[0862], Fig. 45A–C |
| Lipid 11-A-M DC65619 | Intravenous Mouse IV study: 11-A-M nanoparticles supported GFP silencing in splenic T cells at 0.5 mg/kg siRNA. | [10] Source Figure 4C–D |
| 113-AA-C8C14 DC60942 | Intravenous The B-2 formulation of 113-AA-C8C14 was used for systemic CD19-CAR mRNA delivery and T-cell engineering in mice. Its activity is formulation-specific. | [11] Source Main CAR-T experiments; SI Fig. S12 |
| TE-EP8-S DC60578 | Intravenous Systemic mouse study: one-component TE-EP8-S nanoparticles supported functional mRNA delivery to splenic T cells. | [12] Source Abstract; Figure 4 Cre/lox reporter assay |
| 1-A-N DC67121 | Intravenous 1-A-N LNPs carrying siCD45 produced significant CD45 silencing in mouse splenic T cells after systemic administration. | [10] Source SI Fig. S7D,E |
| L829 DC60860 | Intravenous CICL-1/L829 LNPs conjugated to anti-CD5 antibody delivered mCherry mRNA to splenic T cells after intravenous administration in mice. Targeting depends on the antibody-functionalized formulation. | [7] Source Example 66, Fig. 1A; anti-CD5 tLNP, mouse tail-vein dose, splenic T-cell mCherry expression |
| In vivo and ex vivo primary T-cell delivery | ||
| Lipid PL40 DC67553 | Intravenous; ex vivo primary T-cell transfection PL40 LNPs delivered reporter and uPAR CAR RNA to T cells, including systemic in vivo CAR-T experiments; primary human T-cell transfection was tested separately. | [13] Source Figs. 1F, 2C, 4–6 |
| Sanofi Lipid 15 DC67601 | Intravenous; primary human PBMC assays Anti-CD8 VHH-functionalized Lipid 15 LNPs delivered CD22-CAR mRNA to primary human CD8+ T cells and reprogrammed CD8+ T cells in humanized mice. Targeting depends on the complete formulation. | [14] Source Targeted T-cell assays and in vivo CAR experiments |
| 93-O17S DC53130 | Intravenous; ex vivo primary T-cell assays 93-O17S LNPs delivered Cre mRNA in mice, producing reporter recombination in splenic CD4+ and CD8+ T cells; ex vivo primary T-cell reporter delivery was also measured. | [5] Source Figs. 3C, 10C and T-cell Cre-recombination results |
| Lipid Trp-L1-T4 DC68057 | Intravenous; primary mouse Tfh assays Trp-L1-T4-based, CXCR5-antibody-functionalized RLNPs supported saRNA expression and CAR reprogramming in follicular helper T cells. Selectivity also depends on the RNA design. | [15] Source Main Fig. 3B,C,I,J and in vivo treatment experiments |
In vivo and ex vivo results refer to the specified primary T-cell population and formulation. Antibody targeting or other formulation features are stated where required.