Efficient Delivery of Antibody Into Living Cells Using Hemagglutinating Virus of Japan (HVJ) Envelope

Kondo, Yoshitaka; Miyata, Keizo; Kato, Fuminori

doi:10.1002/0471142735.im0216s89

Cited by 3 publications

(4 citation statements)

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“…12,13 Building on that work we show a new strategy for uptake of cell-penetrating nanoconstructs that make nuclear localization of macromolecular IgG antibodies more efficient and controllable. Diverse delivery vehicles like liposomes, 5 cell-penetrating peptides (CPPs), 14 polymer constructs, 15 or viral vectors 16 have been established to facilitate transport of macromolecules across the cellular membrane. In these methods, the delivery efficacy of the vehicles is often dependent on the structure of the target molecule and the cell type.…”

Section: Introductionmentioning

confidence: 99%

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Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67

et al. 2015

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The selective inhibition of intracellular and nuclear molecules such as Ki-67 holds great promise for the treatment of cancer and other diseases. However, the choice of the target protein and the intracellular delivery of the functional agent remain crucial challenges. Main hurdles are (a) an effective delivery into cells, (b) endosomal escape of the delivered agents, and (c) an effective, externally triggered destruction of cells. Here we show a light-controlled two-step approach for selective cellular delivery and cell elimination of proliferating cells. Three different cell-penetrating nano constructs, including liposomes, conjugates with the nuclear localization sequence (NLS), and conjugates with the cell penetrating peptide Pep-1, delivered the light activatable antibody conjugate TuBB-9-FITC, which targets the proliferation associated protein Ki-67. HeLa cells were treated with the photosensitizer benzoporphyrin monoacid derivative (BPD) and the antibody constructs. In the first optically controlled step, activation of BPD at 690 nm triggered a controlled endosomal escape of the TuBB-9-FITC constructs. In more than 75% of Ki-67 positive, irradiated cells TuBB-9-FITC antibodies relocated within 24 h from cytoplasmic organelles to the cell nucleus and bound to Ki-67. After a second light irradiation at 490 nm, which activated FITC, cell viability decreased to approximately 13%. Our study shows an effective targeting strategy, which uses light-controlled endosomal escape and the light inactivation of Ki-67 for cell elimination. The fact that liposomal or peptide-assisted delivery give similar results leads to the additional conclusion that an effective mechanism for endosomal escape leaves greater variability for the choice of the delivery agent.

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Section: Introductionmentioning

confidence: 99%

“…Diverse delivery vehicles like liposomes, cell-penetrating peptides (CPPs), polymer constructs, or viral vectors have been established to facilitate transport of macromolecules across the cellular membrane. In these methods, the delivery efficacy of the vehicles is often dependent on the structure of the target molecule and the cell type.…”

Section: Introductionmentioning

confidence: 99%

Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67

et al. 2015

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“…HVJ-E vectors have been shown to have superior performance in transferring genes into tissues of animals as well as into various cultured cell lines [25][26][27][28][29][30][31]. The vector kit employs delivery principles that are distinctively different from those of cationic non-viral vectors, which are aggressively marketed, and it enables effective intracellular delivery of negatively charged plasmid DNAs, low molecular weight nucleic acids (siRNA, miRNA, antisense/decoy oligonucleotides), and biologically active substances such as peptide proteins (including antibodies) with various electric charges (isoelectric points) [32][33][34][35][36]. These delivery principles (Figure 1), features, procedures, and application examples have been outlined in our previous publications [21,23,27,28,32], and the vector kit is commercially available in both Japan [37] and USA [38].…”

Section: Delivery To Transfection-resistant Non-adherent Immune Cellsmentioning

confidence: 99%

Hemagglutinating Virus of Japan Envelope Vectors as High-Performance Vehicles for Delivery of Small RNAs

Kato¹,

Yagi²,

Fujieda³

et al. 2013

J Genet Syndr Gene Ther

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Hemagglutinating virus of Japan envelope (HVJ-E) vectors are particulate forms of the Sendai virus, and are characterized by maintained cell membrane fusion activities and completely inactivated genomes. HVJ-E vectors can be safely used as a non-viral transfection tools for laboratory research without the need for special protocols or equipment. HVJ-E particles are loaded with molecules such as DNA, proteins, antisense oligonucleotides, or small RNAs, to form HVJ-E vectors that carry these molecules into target cells by virtue of their membrane fusion activity. Interference by small RNAs such as small interfering RNA (siRNA) and microRNA (miRNA) is now established as an important biological strategy for gene silencing, and is becoming an essential method for analyzing biological processes. Various delivery reagents are currently available globally; however, delivery to non-adherent immune cells, particularly primary immune cells, remains extremely difficult. The simple and effective delivery capabilities of HVJ-E vectors overcome the above obstacle. Here we describe examples and demonstrate the utility and potential applications of HVJ-E vectors as high-performance vehicles for delivery of small RNAs.

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“…The HVJ-E particle is prepared by inactivating the wild-type virus (HVJ) by treatment with an alkylating agent and UV irradiation [52,53]. HVJ-E was originally developed as a drug delivery system (vector) for various biopharmaceuticals such as plasmid DNAs, siRNAs, decoy oligonucleotides, antibody proteins, and anticancer drugs [52,[68][69][70][71][72][73][74][75].…”

Section: Non-replicating Virus Particles As Anti-cancer Agentsmentioning

confidence: 99%

A Novel Therapy for Melanoma and Prostate Cancer Using a Non-Replicating Sendai Virus Particle (HVJ-E)

Nakajima¹,

Itai²,

Wada³

et al. 2013

Novel Gene Therapy Approaches

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An alternative option to avoid such a risk is to use a non-replicating oncolytic virus [44]. We found that a non-replicating oncolytic virus (HVJ-E: hemagglutinating virus of Japanenvelope) is able to induce cancer cell-specific apoptosis and immunity [45]. The induction of apoptosis and activation of dendritic cells in vitro, and anti-tumor activity in vivo are similar to the wild-type hemagglutinating virus of Japan (also known as Sendai virus, HVJ) [45]. The hemagglutinating virus of Japan was discovered in Sendai, Japan, in the 1950s [46]. It is a paramyxovirus with a minus-strand RNA genome. The virus has fusogenic activity [47, 48], and is used to prepare hybridoma cells for the production of monoclonal antibodies, and heterokaryons for chromosome analysis [49-51]. The hemagglutinating virus of Japan-envelope is an inactivated HVJ particle [52]. It is manufactured by a process similar to that used for whole virus particle vaccines. Good manufacturing practice (GMP)-regulated processes have been established in their production for use in preclinical and clinical studies [53]. We conducted dose-setting efficacy studies for HVJ-E in a murine cancer model in which dosedependent anti-cancer activity was observed. We also conducted safety studies following good laboratory practices (GLP), including pharmacological safety studies and toxicokinetic (TK) studies in rats and monkeys, as part of an investigational new drug (IND) application. Osaka University Hospital is currently conducting two investigational clinical studies with HVJ-E for the treatment of advanced melanoma and castration-resistant prostate cancer (CRPC) [54-56]. These clinical trials are the first human studies for HVJ-E and will reveal the safety and efficacy of the non-replicating virus (HVJ-E). Virotherapy with a non-replicating oncolytic virus is a new approach that is anticipated to provide a new strategy for cancer therapy. 2. A new strategy for cancer therapy Most cancers are still incurable and new approaches are required to improve the efficacy of cancer treatments. However, conventional cancer therapies are problematic. Chemotherapy with anti-cancer agents is useful in achieving tumor regression. However, the immune system, which is important in the removal of residual cancer cells, is also suppressed by these agents (Figure 1). Therefore, surviving cancer cells and cancer stem cells (CSC) eventually acquire drug resistance, resulting in tumor relapse (Figure 1) [57]. Thus, chemotherapy with cytotoxic drugs does not generally result in the necessary eradication of cancer cells required for long-term survival. Immune therapies for cancer offer a new approach to cancer treatment, and several products, including sipuleucel-T, are currently approved in advanced countries [58, 59]. The aim of these therapies is the removal of cancers by the immune system. Numerous cancer immune therapies are currently under evaluation in clinical studies. However, these agents are not potent because of lack of cytotoxic effect on cancer cells (Figure 1).

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Efficient Delivery of Antibody Into Living Cells Using Hemagglutinating Virus of Japan (HVJ) Envelope

Abstract: This unit describes a novel method for antibody delivery into living cells using HVJ (hemagglutinating virus of Japan) envelope, an inactivated Sendai virus particle.

Cited by 3 publications

References 7 publications

Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67

Light-Controlled Delivery of Monoclonal Antibodies for Targeted Photoinactivation of Ki-67

Hemagglutinating Virus of Japan Envelope Vectors as High-Performance Vehicles for Delivery of Small RNAs

A Novel Therapy for Melanoma and Prostate Cancer Using a Non-Replicating Sendai Virus Particle (HVJ-E)

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