Targeted delivery of genome editors in vivo

Levesque, S. & Bauer, D. E. CRISPR-based therapeutic genome editing for inherited blood disorders. Nat. Rev. Drug Discov. https://doi.org/10.1038/s41573-025-01236-y (2025).
Google Scholar
Raguram, A., Banskota, S. & Liu, D. R. Therapeutic in vivo delivery of gene editing agents. Cell 185, 2806–2827 (2022).
Google Scholar
Tsuchida, C. A., Wasko, K. M., Hamilton, J. R. & Doudna, J. A. Targeted nonviral delivery of genome editors in vivo. Proc. Natl Acad. Sci. USA 121, e2307796121 (2024).
Google Scholar
Stigzelius, V., Cavallo, A. L., Chandode, R. K. & Nitsch, R. Peeling back the layers of immunogenicity in Cas9-based genomic medicine. Mol. Ther. 33, 4714–4730 (2025).
Google Scholar
Porteus, M. Genome editing: a new approach to human therapeutics. Annu. Rev. Pharmacol. Toxicol. 56, 163–190 (2014).
Google Scholar
Kumar, M., Kulkarni, P., Liu, S., Chemuturi, N. & Shah, D. K. Nanoparticle biodistribution coefficients: a quantitative approach for understanding the tissue distribution of nanoparticles. Adv. Drug Deliv. Rev. 194, 114708 (2023).
Google Scholar
Gillmore, J. D. et al. CRISPR–Cas9 in vivo gene editing for transthyretin amyloidosis. N. Engl. J. Med. 385, 493–502 (2021).
Google Scholar
Musunuru, K. et al. Patient-specific in vivo gene editing to treat a rare genetic disease. N. Engl. J. Med. 392, 2235–2243 (2025).
Google Scholar
Horie, T. & Ono, K. VERVE-101: a promising CRISPR-based gene editing therapy that reduces LDL-C and PCSK9 levels in HeFH patients. Eur. Heart J. Cardiovasc. Pharmacother. 10, 89–90 (2023).
Google Scholar
Cohn, D. M. et al. CRISPR-based therapy for hereditary angioedema. N. Engl. J. Med. 392, 458–467 (2025).
Google Scholar
Lee, R. et al. An investigational in vivo base editing medicine targeting ANGPTL3, VERVE-201, achieves precise and durable liver editing in nonclinical studies. Atherosclerosis 395, 118496 (2024).
Google Scholar
Beam Therapeutics. A phase 1/2 dose-exploration and dose-expansion study to evaluate the safety and efficacy of BEAM-302 in adult patients with α-1 antitrypsin deficiency (AATD)-associated lung disease and/or liver disease. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06389877 (2024).
Morrow, P. K. et al. Abstract 17013: CTX320: an investigational in vivo CRISPR-based therapy efficiently and durably reduces lipoprotein (a) levels in non-human primates after a single dose. Circulation 148, A17013 (2023).
HuidaGene Therapeutics. An investigator-initiated clinical study evaluating the CRISPR–hfCas12Max gene editing therapy in the treatment of Duchenne muscular dystrophy (DMD). ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06594094 (2024).
Beam Therapeutics. A phase 1/2, dose-exploration study to evaluate the safety and efficacy of BEAM-301 in patients with glycogen storage disease type Ia (GSDIa) homozygous or compound heterozygous for the G6PC1 c.247C>T (p.R83C) variant. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06735755 (2024).
Arbor Biotechnologies. A phase 1/2 dose escalation study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of ABO-101 in participants with primary hyperoxaluria type 1 (PH1). ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06839235 (2025).
Tune Therapeutics. Phase 1b multicenter, open-label study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of Tune-401 in participants with chronic hepatitis B infection. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06671093 (2024).
Burdo, T. H. et al. Preclinical safety and biodistribution of CRISPR targeting SIV in non-human primates. Gene Ther. 31, 224–233 (2023).
Google Scholar
Excision BioTherapeutics. A phase 1/2a, sequential cohort, single ascending dose study of the safety, tolerability, biodistribution, and pharmacodynamics of EBT 101 in aviremic HIV-1 infected adults on stable antiretroviral therapy. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT05144386 (2021).
Epicrispr Biotechnologies. A phase 1/2 open-label dose-escalation study to evaluate the safety, tolerability, and biological activity of EPI-321, an AAVrh74-delivered epigenetic editing therapy in adult FSHD patients. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06907875 (2025).
Streilein, J. W. Ocular immune privilege: therapeutic opportunities from an experiment of nature. Nat. Rev. Immunol. 3, 879–889 (2003).
Google Scholar
Nakao, S., Hafezi-Moghadam, A. & Ishibashi, T. Lymphatics and lymphangiogenesis in the eye. J. Ophthalmol. 2012, 783163 (2012).
Google Scholar
Toral, M. A. et al. Investigation of Cas9 antibodies in the human eye. Nat. Commun. 13, 1053 (2022).
Google Scholar
Pierce, E. A. et al. Gene editing for CEP290-associated retinal degeneration. N. Engl. J. Med. 390, 1972–1984 (2024).
Google Scholar
Zhao, Q., Wei, L. & Chen, Y. From bench to bedside: developing CRISPR/Cas-based therapy for ocular diseases. Pharmacol. Res. 213, 107638 (2025).
Google Scholar
Muller, A. et al. High-efficiency base editing in the retina in primates and human tissues. Nat. Med. 31, 490–501 (2025).
Google Scholar
Luk, A. et al. World’s first CRISPR/RNA-targeting therapy (HG202) for patients with neovascular age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 65, 4357 (2024).
Wei, A. et al. In vivo CRISPR gene editing in patients with herpetic stromal keratitis. Mol. Ther. 31, 3163–3175 (2023).
Google Scholar
Jain, A. et al. CRISPR–Cas9–based treatment of myocilin-associated glaucoma. Proc. Natl Acad. Sci. USA 114, 11199–11204 (2017).
Google Scholar
Gencay, Y. E. et al. Engineered phage with antibacterial CRISPR–Cas selectively reduce E. coli burden in mice. Nat. Biotechnol. 42, 265–274 (2024).
Google Scholar
SNIPR Biome. A phase 1, randomized, double-blind, first-in-human, dose escalation study investigating the safety, recovery, and pharmacodynamics of multiple oral administrations of SNIPR001 in healthy subjects. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT05277350 (2022).
SNIPR Biome. SNIPR Biome Reports Positive Clinical Interim Results for Groundbreaking, First-in-Human, CRISPR-Based Microbial Gene Therapy https://static1.squarespace.com/static/5bacc67990f9041ab0d5b0c1/t/6476ee0c6181141d414b9ec3/1685515789399/230529+SNIPR+Phase+1+Data+Release.pdf (2023).
Xue, Y. et al. RNA base editing therapy cures hearing loss induced by OTOF gene mutation. Mol. Ther. 31, 3520–3530 (2023).
Google Scholar
HuidaGene Therapeutics. An open-label, multiple-cohort, dose-finding, investigator-initiated trial to evaluate the safety, tolerability, and efficacy of HG205 RNA base-editing therapy in subjects with OTOF-p.Q829X mutation-associated hearing loss. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06025032 (2023).
Yang, D. et al. An RNA editing strategy rescues gene duplication in a mouse model of MECP2 duplication syndrome and nonhuman primates. Nat. Neurosci. 28, 72–83 (2025).
Google Scholar
HuidaGene Therapeutics. An open-label, multiple-dose clinical study to evaluating the safety, tolerability and preliminary efficacy of a single intracerebroventricular injection of HG204 for the treatment of MECP2 duplication syndrome. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06615206 (2024).
Lenneman, B. R., Fernbach, J., Loessner, M. J., Lu, T. K. & Kilcher, S. Enhancing phage therapy through synthetic biology and genome engineering. Curr. Opin. Biotechnol. 68, 151–159 (2021).
Google Scholar
Kim, P. et al. Safety, pharmacokinetics, and pharmacodynamics of LBP-EC01, a CRISPR–Cas3-enhanced bacteriophage cocktail, in uncomplicated urinary tract infections due to Escherichia coli (ELIMINATE): the randomised, open-label, first part of a two-part phase 2 trial. Lancet Infect. Dis. 24, 1319–1332 (2024).
Google Scholar
Amoasii, L. et al. Single-cut genome editing restores dystrophin expression in a new mouse model of muscular dystrophy. Sci. Transl. Med. 9, eaan8081 (2017).
Google Scholar
Ho, T.-C. et al. Scaffold-mediated CRISPR–Cas9 delivery system for acute myeloid leukemia therapy. Sci. Adv. 7, eabg3217 (2021).
Google Scholar
Liang, S.-Q. et al. AAV5 delivery of CRISPR–Cas9 supports effective genome editing in mouse lung airway. Mol. Ther. 30, 238–243 (2022).
Google Scholar
Rosenblum, D. et al. CRISPR–Cas9 genome editing using targeted lipid nanoparticles for cancer therapy. Sci. Adv. 6, eabc9450 (2020).
Google Scholar
Stahl, E. C. et al. Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs. Mol. Ther. 31, 2422–2438 (2023).
Google Scholar
Kasiewicz, L. N. et al. GalNAc-lipid nanoparticles enable non-LDLR dependent hepatic delivery of a CRISPR base editing therapy. Nat. Commun. 14, 2776 (2023).
Google Scholar
Lee, R. et al. An investigational in vivo base editing medicine targeting ANGPTL3, VERVE-201, achieves potent and LDLR-independent liver editing in mouse models. Eur. Heart J. 44, ehad655.2521 (2023).
Google Scholar
Verve Therapeutics. A phase 1b single ascending dose study to evaluate the safety of VERVE-201 in patients with refractory hyperlipidemia. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06451770 (2024).
Pupo, A. et al. AAV vectors: the Rubik’s cube of human gene therapy. Mol. Ther. 30, 3515–3541 (2022).
Google Scholar
Gao, G.-P. et al. Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc. Natl Acad. Sci. USA 99, 11854–11859 (2002).
Google Scholar
Strebinger, D. et al. Cell type-specific delivery by modular envelope design. Nat. Commun. 14, 5141 (2023).
Google Scholar
Hamilton, J. R. et al. In vivo human T cell engineering with enveloped delivery vehicles. Nat. Biotechnol. 42, 1684–1692 (2024).
Google Scholar
Hamilton, J. R. et al. Targeted delivery of CRISPR–Cas9 and transgenes enables complex immune cell engineering. Cell Rep. 35, 109207 (2021).
Google Scholar
Ngo, W. et al. Mechanism-guided engineering of a minimal biological particle for genome editing. Proc. Natl Acad. Sci. USA 122, e2413519121 (2025).
Google Scholar
Karp, H. et al. Packaged delivery of CRISPR–Cas9 ribonucleoproteins accelerates genome editing. Nucleic Acids Res. 53, gkaf105 (2025).
Google Scholar
Breda, L. et al. In vivo hematopoietic stem cell modification by mRNA delivery. Science 381, 436–443 (2023).
Google Scholar
Palanki, R. et al. In utero delivery of targeted ionizable lipid nanoparticles facilitates in vivo gene editing of hematopoietic stem cells. Proc. Natl Acad. Sci. USA 121, e2400783121 (2024).
Google Scholar
Geczy, R. et al. Lipid nanoparticle-mediated gene editing of human primary T cells and off-target analysis of the CRISPR–Cas9 indels. Blood 142, 6833 (2023).
Google Scholar
Dilliard, S. A., Cheng, Q. & Siegwart, D. J. On the mechanism of tissue-specific mRNA delivery by selective organ targeting nanoparticles. Proc. Natl Acad. Sci. USA 118, e2109256118 (2021).
Google Scholar
Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue specific mRNA delivery and CRISPR/Cas gene editing. Nat. Nanotechnol. 15, 313–320 (2020).
Google Scholar
Chen, K. et al. Lung and liver editing by lipid nanoparticle delivery of a stable CRISPR–Cas9 ribonucleoprotein. Nat. Biotechnol. 43, 1445–1457 (2025).
Google Scholar
Kimura, S. & Harashima, H. On the mechanism of tissue-selective gene delivery by lipid nanoparticles. J. Control. Release 362, 797–811 (2023).
Google Scholar
Tabebordbar, M. et al. Directed evolution of a family of AAV capsid variants enabling potent muscle-directed gene delivery across species. Cell 184, 4919–4938 (2021).
Google Scholar
Huang, Q. et al. An AAV capsid reprogrammed to bind human transferrin receptor mediates brain-wide gene delivery. Science 384, 1220–1227 (2024).
Google Scholar
Neumann, E. N. et al. Brainwide silencing of prion protein by AAV-mediated delivery of an engineered compact epigenetic editor. Science 384, ado7082 (2024).
Google Scholar
Kumar, S. R. et al. Multiplexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types. Nat. Methods 17, 541–550 (2020).
Google Scholar
Kim, H. et al. Lipid nanoparticle-mediated mRNA delivery to CD34+ cells in rhesus monkeys. Nat. Biotechnol. 43, 1813–1820 (2024).
Google Scholar
Dahlman, J. E. et al. Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics. Proc. Natl Acad. Sci. USA 114, 2060–2065 (2017).
Google Scholar
Ngo, W. et al. Why nanoparticles prefer liver macrophage cell uptake in vivo. Adv. Drug Deliv. Rev. 185, 114238 (2022).
Google Scholar
Glaumann, H., Fredzell, J., Jubner, A. & Ericsson, J. L. E. Uptake and degradation of glycogen by Kupffer cells. Exp. Mol. Pathol. 31, 70–80 (1979).
Google Scholar
Seo, J. W. et al. Multimodal imaging of capsid and cargo reveals differential brain targeting and liver detargeting of systemically-administered AAVs. Biomaterials 288, 121701 (2022).
Google Scholar
l’Hortet, A. C. et al. In MDA Clinical & Scientific Conference 206 https://www.mdaconference.org/abstract-library/epi-321-a-potential-cure-for-fshd/ (Muscular Dystrophy Association, 2023).
Amoasii, L. et al. Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science 362, 86–91 (2018).
Google Scholar
Vaessen, S. F. C. et al. AAV gene therapy as a means to increase apolipoprotein (Apo) A-I and high-density lipoprotein-cholesterol levels: correction of murine ApoA-I deficiency. J. Gene Med. 11, 697–707 (2009).
Google Scholar
Prasad, K.-M. R., Xu, Y., Yang, Z., Acton, S. T. & French, B. A. Robust cardiomyocyte-specific gene expression following systemic injection of AAV: in vivo gene delivery follows a Poisson distribution. Gene Ther. 18, 43–52 (2011).
Google Scholar
Radhiyanti, P. T., Konno, A., Matsuzaki, Y. & Hirai, H. Comparative study of neuron-specific promoters in mouse brain transduced by intravenously administered AAV-PHP.eB. Neurosci. Lett. 756, 135956 (2021).
Google Scholar
Yang, L. et al. MicroRNA-122-mediated liver detargeting enhances the tissue specificity of cardiac genome editing. Circulation 149, 1778–1781 (2024).
Google Scholar
Hoffmann, M. D. et al. Cell-specific CRISPR–Cas9 activation by microRNA-dependent expression of anti-CRISPR proteins. Nucleic Acids Res. 47, e75 (2019).
Google Scholar
Hirosawa, M., Fujita, Y. & Saito, H. Cell-type-specific CRISPR activation with microRNA-responsive AcrllA4 switch. ACS Synth. Biol. 8, 1575–1582 (2019).
Google Scholar
Lee, J. et al. Tissue-restricted genome editing in vivo specified by microRNA-repressible anti-CRISPR proteins. RNA 25, 1421–1431 (2019).
Google Scholar
Wang, X.-W. et al. A microRNA-inducible CRISPR–Cas9 platform serves as a microRNA sensor and cell-type-specific genome regulation tool. Nat. Cell Biol. 21, 522–530 (2019).
Google Scholar
Garcia-Guerra, A. et al. Tissue-specific modulation of CRISPR activity by miRNA-sensing guide RNAs. Nucleic Acids Res. 53, gkaf016 (2025).
Google Scholar
Galizi, R. & Jaramillo, A. Engineering CRISPR guide RNA riboswitches for in vivo applications. Curr. Opin. Biotechnol. 55, 103–113 (2019).
Google Scholar
Kaseniit, K. E. et al. Modular, programmable RNA sensing using ADAR editing in living cells. Nat. Biotechnol. 41, 482–487 (2023).
Google Scholar
Jiang, K. et al. Programmable eukaryotic protein synthesis with RNA sensors by harnessing ADAR. Nat. Biotechnol. 41, 698–707 (2023).
Google Scholar
Qian, Y. et al. Programmable RNA sensing for cell monitoring and manipulation. Nature 610, 713–721 (2022).
Google Scholar
Powell, S. K., Rivera-Soto, R. & Gray, S. J. Viral expression cassette elements to enhance transgene target specificity and expression in gene therapy. Discov. Med. 19, 49–57 (2015).
Google Scholar
Mancuso, P. et al. CRISPR based editing of SIV proviral DNA in ART treated non-human primates. Nat. Commun. 11, 6065 (2020).
Google Scholar
Cohrt, K. O. Excision’s EBT-101 demonstrates safety in clinical trial but does not cure HIV. CRISPR Medicine News https://crisprmedicinenews.com/news/excisions-ebt-101-demonstrates-safety-in-clinical-trial-but-does-not-cure-hiv/ (2024).
Tan, I.-L. et al. Targeting the non-coding genome and temozolomide signature enables CRISPR-mediated glioma oncolysis. Cell Rep. 42, 113339 (2023).
Google Scholar
An, Y. et al. Design of hypoxia responsive CRISPR–Cas9 for target gene regulation. Sci. Rep. 13, 16763 (2023).
Google Scholar
Chen, X., Chen, Y., Xin, H., Wan, T. & Ping, Y. Near-infrared optogenetic engineering of photothermal nanoCRISPR for programmable genome editing. Proc. Natl Acad. Sci. USA 117, 2395–2405 (2020).
Google Scholar
Yin, H. et al. Ultrasound-controlled CRISPR/Cas9 system augments sonodynamic therapy of hepatocellular carcinoma. ACS Cent. Sci. 7, 2049–2062 (2021).
Google Scholar
Liu, Y. et al. Very fast CRISPR on demand. Science 368, 1265–1269 (2020).
Google Scholar
Pacesa, M. et al. Structural basis for Cas9 off-target activity. Cell 185, 4067–4081 (2022).
Google Scholar
Greig, J. A. et al. Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration. Nat. Biotechnol. 42, 1232–1242 (2024).
Google Scholar
iECURE. A phase 1/2/3 first-in-human, open-label, dose-escalation study to evaluate the safety and efficacy of a single intravenous (IV) administration of ECUR-506 in males less than 9 months of age with genetically confirmed neonatal onset ornithine transcarbamylase (OTC) deficiency. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06255782 (2023).
Regeneron Pharmaceuticals. A two-part open-label study of REGV131-LNP1265, a CRISPR/Cas9 based coagulation factor IX gene insertion therapy in participants with hemophilia B. ClinicalTrials.gov https://clinicaltrials.gov/study/NCT06379789 (2024).
Jeune, V. L., Joergensen, J. A., Hajjar, R. J. & Weber, T. Pre-existing anti-adeno-associated virus antibodies as a challenge in AAV gene therapy. Hum. Gene Ther. Methods 24, 59–67 (2013).
Google Scholar
Duan, D. Lethal immunotoxicity in high-dose systemic AAV therapy. Mol. Ther. 31, 3123–3126 (2023).
Google Scholar
Lee, Y., Jeong, M., Park, J., Jung, H. & Lee, H. Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics. Exp. Mol. Med. 55, 2085–2096 (2023).
Google Scholar
Vargas, J. E. et al. Retroviral vectors and transposons for stable gene therapy: advances, current challenges and perspectives. J. Transl. Med. 14, 288 (2016).
Google Scholar
Wignakumar, T. & Fairchild, P. J. Evasion of pre-existing immunity to Cas9: a prerequisite for successful genome editing in vivo? Curr. Transplant. Rep. 6, 127–133 (2019).
Google Scholar
Kishimoto, T. K. & Samulski, R. J. Addressing high dose AAV toxicity — ‘one and done’ or ‘slower and lower’? Expert Opin. Biol. Ther. 22, 1067–1071 (2022).
Google Scholar
Cullis, P. R. & Hope, M. J. Lipid nanoparticle systems for enabling gene therapies. Mol. Ther. 25, 1467–1475 (2017).
Google Scholar
Cullis, P. R. & Felgner, P. L. The 60-year evolution of lipid nanoparticles for nucleic acid delivery. Nat. Rev. Drug Discov. 23, 709–722 (2024).
Google Scholar
Carbonaro-Sarracino, D. A. et al. Dosing and re-administration of intravenous lentiviral vector for liver-directed gene transfer in young rhesus monkeys and ADA-deficient mice. Mol. Ther. Methods Clin. Dev. 24, S302–S303 (2016).
Chen, K. et al. Engineering self-deliverable ribonucleoproteins for genome editing in the brain. Nat. Commun. 15, 1727 (2024).
Google Scholar
Staahl, B. T. et al. Efficient genome editing in the mouse brain by local delivery of engineered Cas9 ribonucleoprotein complexes. Nat. Biotechnol. 35, 431–434 (2017).
Google Scholar
Chew, W. L. Immunity to CRISPR Cas9 and Cas12a therapeutics. Wiley Interdiscip. Rev. Syst. Biol. Med. https://doi.org/10.1002/wsbm.1408 (2018).
Andari, J. E. & Grimm, D. Production, processing, and characterization of synthetic AAV gene therapy vectors. Biotechnol. J. 16, e2000025 (2021).
Google Scholar
Jiang, Z. & Dalby, P. A. Challenges in scaling up AAV-based gene therapy manufacturing. Trends Biotechnol. 41, 1268–1281 (2023).
Google Scholar
De, A. & Ko, Y. T. Why mRNA-ionizable LNPs formulations are so short-lived: causes and way-out. Expert Opin. Drug Deliv. 20, 175–187 (2023).
Google Scholar
Kim, B. et al. Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines. J. Control. Release 353, 241–253 (2023).
Google Scholar
Mangeot, P. E. et al. Genome editing in primary cells and in vivo using viral-derived Nanoblades loaded with Cas9–sgRNA ribonucleoproteins. Nat. Commun. 10, 45 (2019).
Google Scholar
Merten, O.-W., Hebben, M. & Bovolenta, C. Production of lentiviral vectors. Mol. Ther. Methods Clin. Dev. 3, 16017 (2016).
Google Scholar
Binder, G. K. & Chen, C.-C. The very stable lentiviral vector. Mol. Ther. Methods Clin. Dev. 32, 101223 (2024).
Google Scholar
Berry, G. E. & Asokan, A. Cellular transduction mechanisms of adeno-associated viral vectors. Curr. Opin. Virol. 21, 54–60 (2016).
Google Scholar
Patel, M. N. et al. Safer non-viral DNA delivery using lipid nanoparticles loaded with endogenous anti-inflammatory lipids. Nat. Biotechnol. https://doi.org/10.1038/s41587-025-02556-5 (2025).
Google Scholar
Banskota, S. et al. Engineered virus-like particles for efficient in vivo delivery of therapeutic proteins. Cell 185, 250–265 (2022).
Google Scholar
An, M. et al. Engineered virus-like particles for transient delivery of prime editor ribonucleoprotein complexes in vivo. Nat. Biotechnol. 42, 1526–1537 (2024).
Google Scholar
Lyu, P., Javidi-Parsijani, P., Atala, A. & Lu, B. Delivering Cas9/sgRNA ribonucleoprotein (RNP) by lentiviral capsid-based bionanoparticles for efficient ‘hit-and-run’ genome editing. Nucleic Acids Res. 47, e99 (2019).
Google Scholar
Indikova, I. & Indik, S. Highly efficient ‘hit-and-run’ genome editing with unconcentrated lentivectors carrying Vpr.Prot.Cas9 protein produced from RRE-containing transcripts. Nucleic Acids Res. 48, 8178–8187 (2020).
Google Scholar
Gao, G., Vandenberghe, L. H. & Wilson, J. M. New recombinant serotypes of AAV vectors. Curr. Gene Ther. 5, 285–297 (2005).
Google Scholar
Pham, Q. et al. A facile chemical strategy to synthesize precise AAV-protein conjugates for targeted gene delivery. Mol. Ther. Oncol. 33, 201040 (2025).
Google Scholar
Domenger, C. & Grimm, D. Next-generation AAV vectors—do not judge a virus (only) by its cover. Hum. Mol. Genet. 28, R3–R14 (2019).
Google Scholar
Billingsley, M. M. et al. In vivo mRNA CAR T cell engineering via targeted ionizable lipid nanoparticles with extrahepatic tropism. Small 20, e2304378 (2024).
Google Scholar
Rurik, J. G. et al. CAR T cells produced in vivo to treat cardiac injury. Science 375, 91–96 (2022).
Google Scholar
Veiga, N. et al. Cell specific delivery of modified mRNA expressing therapeutic proteins to leukocytes. Nat. Commun. 9, 4493 (2018).
Google Scholar
Dobson, C. S. et al. Antigen identification and high-throughput interaction mapping by reprogramming viral entry. Nat. Methods 19, 449–460 (2022).
Google Scholar
Girard-Gagnepain, A. et al. Baboon envelope pseudotyped LVs outperform VSV-G-LVs for gene transfer into early-cytokine-stimulated and resting HSCs. Blood 124, 1221–1231 (2014).
Google Scholar
Seydel, C. Spotlight Therapeutics: making CRISPR deliver in vivo. Nat. Biotechnol. https://doi.org/10.1038/d41587-021-00011-9 (2021).
Google Scholar




