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At least 1,081 records · Page 60Linked to original sources
PubMed1997

Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors.

Haemophilia B, or factor IX deficiency, is a X-linked recessive disorder that occurs in about one in 25,000 males, and severely affected people are at risk for spontaneous bleeding into numerous organs. Bleeding can be life-threatening or lead to chronic disabilities with haemophilic arthropathy. The severity of the bleeding tendency varies among patients and is related to the concentration of functional plasma factor IX. Patients with 5-30% of the normal factor IX have mild haemophilia that may not be recognized until adulthood or after heavy trauma or surgery. Therapy for acute bleeding consists of the transfusion of clotting-factor concentrates prepared from human blood and recombinant clotting factors that are currently in clinical trials. Both recombinant retroviral and adenoviral vectors have successfully transferred factor IX cDNA into the livers of dogs with haemophilia B. Recombinant retroviral-mediated gene transfer results in persistent yet subtherapeutic concentrations of factor IX and requires the stimulation of hepatocyte replication before vector administration. Recombinant adenoviral vectors can temporarily cure the coagulation defect in the canine haemophilia B model; however, an immune response directed against viral gene products made by the vector results in toxicity and limited gene expression. The use of recombinant adeno-associated virus (rAAV) vectors is promising because the vector contains no viral genes and can transduce non-dividing cells. The efficacy of in vivo transduction of non-dividing cells has been demonstrated in a wide variety of tissues. In this report, we describe the successful transduction of the liver in vivo using r-AAV vectors delivered as a single administration to mice and demonstrate that persistent, curative concentrations of functional human factor IX can be achieved using wild-type-free and adenovirus-free rAAV vectors. This demonstrates the potential of treating haemophilia B by gene therapy at the natural site of factor IX production.

Alanine Transaminase↗
PubMed1997

Sustained expression of genes delivered directly into liver and muscle by lentiviral vectors.

Successful gene therapy approaches will require efficient gene delivery and sustained expression of the transgene in recipients. A variety of methods, ranging from direct DNA delivery to infection with recombinant viruses containing foreign genes, have been developed, but they all have some major limitations that restrict their utility. We have described a human lentiviral (HIV)-based vector that can transduce non-dividing cells in vitro and deliver genes in vivo. With this vector, expression of transgenes in the brain has been detected for more than six months--the longest period tested so far. Because lentiviral vectors are pseudotyped with vesicular stomatitis virus G glycoprotein (VSVG; ref. 8), they can transduce a broad range of tissues and cell types. We now describe the ability of lentiviral vectors to introduce genes directly into liver and muscle. Sustained expression of green fluorescent protein (GFP), used as a surrogate for therapeutic protein, can be observed for more than 22 weeks in the liver. Similar long-term expression (more than eight weeks) was observed in transduced muscle. In contrast, little or no GFP could be detected in liver or muscle transduced with the Moloney murine leukaemia virus (M-MLV), a prototypic retroviral based vector. At a minimum, 3-4% of the total liver tissue was transduced by a single injection of 1-3 x 10(7) infectious units (I.U.) of recombinant HIV vector. Furthermore, no inflammation of recruitment of lymphocytes could be detected at the site of injection. Animals previously transduced with a lentiviral vector can be efficiently re-infected with lentiviral vectors. Additionally, we show that the requirement for lentiviral accessory proteins to establish efficient transduction in vivo is tissue dependent.

Animals↗
PubMed2000

Highly efficient suicide gene expression in hepatocellular carcinoma cells by epstein-barr virus-based plasmid vectors combined with polyamidoamine dendrimer.

The present study was aimed at devising an efficient nonviral strategy for suicide gene therapy of hepatocellular carcinoma (HCC). To improve the efficiency of DNA delivery and expression, we applied Epstein-Barr virus (EBV)-based plasmid vectors instead of conventional plasmid vectors and combined them with cationic liposome (EBV/lipoplex) or polyamidoamine dendrimer (PAAD) (EBV/polyplex). When the beta-galactosidase gene was transferred to HuH7, PLC/PRF/5, or HLE cells, < or =50-fold higher beta-galactosidase activities were demonstrated in the cells transfected with EBV vector compared with those transfected with conventional plasmid vectors. PAAD-mediated transfection of HCC with pSES.Tk (an EBV-based vector carrying the herpes simplex virus-1 thymidine kinase gene) resulted in a marked reduction in viable cell number by the addition of ganciclovir (GCV). The HCC cells transfected with pSES.Tk/PAAD showed 100- to 1000-fold higher susceptibilities to GCV than those transfected with pS.Tk (a conventional plasmid vector carrying herpes simplex virus-1 thymidine kinase gene)/PAAD. The pSES.Tk-transfected HCC cells were effectively killed by day 9 in culture with a clinically feasible concentration of GCV (25 microM), whereas the pS.Tk-transfected cells survived the culture. These results demonstrate highly efficient suicide gene transfer into various HCC cells by EBV-based plasmid vectors in vitro, suggesting the possible application of this nonviral vector system to gene therapy of HCC.

Antineoplastic Agents↗
PubMed2003

Replicative retroviral vectors for cancer gene therapy.

Poor efficiency of gene transfer into cancer cells constitutes the major bottleneck of current cancer gene therapy. We reasoned that because tumors are masses of rapidly dividing cells, they would be most efficiently transduced with vector systems allowing transgene propagation. We thus designed two replicative retrovirus-derived vector systems: one inherently replicative vector, and one defective vector propagated by a helper retrovirus. In vitro, both systems achieved very efficient transgene propagation. In immunocompetent mice, replicative vectors transduced >85% tumor cells, whereas defective vectors transduced <1% under similar conditions. It is noteworthy that viral propagation could be efficiently blocked by azido-thymidine, in vitro and in vivo. In a model of established brain tumors treated with suicide genes, replicative retroviral vectors (RRVs) were approximately 1000 times more efficient than defective adenoviral vectors. These results demonstrate the advantage and potential of RRVs and strongly support their development for cancer gene therapy.

3T3 Cells↗
PubMed2006

Suppressor of cytokine signaling-1 expression by infectivity-enhanced adenoviral vector inhibits IL-6-dependent proliferation of multiple myeloma cells.

Multiple myeloma (MM) accounts for 10% of hematological malignant disorders. Its refractory nature indicates the necessity of developing novel therapeutic modalities. Since interleukin 6 (IL-6) is one of the major growth factors for MM cells, we expressed suppressor of cytokine signaling-1 (SOCS-1), one of the blockades of IL-6 receptor downstream signaling, to suppress the proliferation of MM cells. Because MM cells are resistant to conventional adenoviral vector infection, we utilized infectivity-enhanced adenoviral vectors with an RGD4C motif in the adenoviral fiber-knob region (RGD-modified vector). In infectivity analysis, RGD-modified vectors were superior to unmodified controls in the majority of the MM cell lines tested. The overexpression of SOCS-1 using infectivity-enhanced adenoviral vectors achieved growth suppression in IL-6-dependent MM cells, but not in the IL-6-independent cells. IL-6-induced STAT3 phosphorylation was suppressed in IL-6-dependent cells, indicating that the signal transduction cascade of the IL-6 receptor signaling was blocked. In aggregate, SOCS-1 overexpression with RGD-modified adenoviral vectors achieved the antiproliferative effect in IL-6-dependent MM cells. These results provide an initial proof-of-principle of the anticancer effect of SOCS-1 expression vector as well as a promise for the future development of therapeutic modality for MM based on this vector.

Adenoviridae↗
PubMed2006

Oncolytic adenoviral vector carrying the cytosine deaminase gene for melanoma gene therapy.

We constructed an oncolytic adenoviral vector Ad.HE1HCD3, in which the adenoviral E1A promoter was replaced by a human tyrosinase enhancer (HTE)/promoter. The RGD-4C peptide was inserted into the HI loop of the fiber knob domain to increase the transduction efficiency of this vector for tumor cell lines. We also inserted the prodrug activating cytosine deaminase gene driven by the HTE/promoter into the E3 region of the Ad.HE1HCD3 vector. The in vitro cytotoxic effect of the Ad.HE1HCD3 vector with 5-fluorocytosine (5-FC) was greater than that of a wild-type adenovirus or that of the Ad.HE1HCD3 vector alone in tyrosinase-positive melanoma cell lines at low multiplicity of infection. Intratumoral injection of low doses of the Ad.HE1HCD3 vector into xenotransplanted human melanoma cell lines followed by the intraperitoneal injection of 5-FC led to a greater degree of tumor regression in vivo than did the intratumoral injection of the same dose of the Ad.HE1HCD3 vector alone. This oncolytic vector with a melanoma-specific prodrug activation therapeutic transcription unit and a RGD targeted fiber protein offers a potent therapeutic combination for the gene therapy of melanoma.

Adenoviridae↗
PubMed2006

Evaluation of adenovirus vectors containing serotype 35 fibers for tumor targeting.

There is growing evidence from in vitro studies that subgroup B adenoviruses (Ad) can overcome the limitations in safety and tumor transduction efficiency seen with commonly used subgroup C serotype 5-based vectors. In this study, we confirm that the expression level of the B-group Ad receptor, CD46, correlates with the grade of malignancy of cervical cancer in situ. We also demonstrate the in vivo properties of Ad5-based vectors that contain the B-group Ad serotype 35 fiber (Ad5/35) in transgenic mice that express CD46 in a pattern and at a level similar to humans. Upon intravenous and intraperitoneal injection, an Ad5/35 vector did not efficiently transduce normal tissue, but was able to target metastatic or intraperitoneal tumors that express CD46 at levels comparable to human tumors. When an oncolytic Ad5/35-based vector was employed, in both tumor models antitumor effects were observed. Furthermore, injection of Ad5/35 vectors into CD46 transgenic mice caused less innate toxicity than Ad5 vectors. Our data demonstrate that Ad vectors that target CD46 offer advantages over Ad5-based vectors for treatment of cancer.

Adenoviridae↗
PubMed1997

Antibody to CD40 ligand inhibits both humoral and cellular immune responses to adenoviral vectors and facilitates repeated administration to mouse airway.

Adenoviral vectors have been used successfully to transfer the human CFTR cDNA to respiratory epithelium in animal models and to CF patients in vivo. However, studies done primarily in mice, indicate that present vector systems have limitations. Among other things, transgene expression in the lung is transient and the production of neutralizing antibodies against adenovirus correlates with a reduced ability to readminister a vector of the same serotype. Here we demonstrate that in mice, a transient blockade of costimulation between activated T cells and B cells/antigen presenting cells using a monoclonal antibody (MR1) against murine CD40 ligand inhibits the development of neutralizing antibodies to adenoviral (Ad) vector. MR1 also decreased the cellular immune response to Ad vector and allowed an increase in persistence of transgene expression. Furthermore, when administered with a second dose of Ad vector to mice preimmunized against vector, MR1 was able to interfere with the development of a secondary antibody response and allowed for high levels of transgene expression upon a third administration of vector to the airway.

Adenoviridae↗
PubMed1997

Tumour immunotherapy using an adenoviral vector expressing a membrane-bound mutant of murine TNF alpha.

The most limiting factor regarding the use of TNF alpha in tumour therapy is systemic toxicity. The expression of membrane-bound (nonsecreted) TNF alpha within a tumour may serve to reduce systemic toxicity while retaining anti-tumour activity. Two adenovirus (Ad) vectors were constructed: (1) Ad-mTNF-wt expressing wild-type murine TNF alpha; and (2) Ad-mTNF-MEM expressing a mutant non-secreted (membrane-bound) form. Only the Ad-mTNF-wt vector induced high levels of TNF alpha secretion in transduced cells (approximately 400 ng/10(6) cells), however, both vectors induced efficient cell surface expression as detected by FACS. These vectors were used in tumour immunotherapy trials in a murine transgenic breast cancer model. High serum concentrations of mTNF alpha (approximately 1 ng/ml) were detected only in Ad-mTNF-wt-treated mice, while both vectors induced substantial disruption of tumour pathology. The wt TNF vector was highly toxic, killing 12 of 16 mice at a dose of 5 x 10(8) p.f.u., whereas the Ad-mTNF-MEM vector showed low toxicity killing three of 27 at the same dose. Both vectors induced partial, and in some cases, permanent tumour regressions, with cured mice displaying protective immunity and specific CTL activity against the tumour. These results indicate that the use of a nonsecreted form of TNF alpha can result in a relatively large reduction in systemic toxicity with little or no reduction in antitumour activity.

Adenoviridae↗
PubMed1998

The selectable marker neo gene down-regulates gene expression from retroviral vectors containing an internal ribosome entry site.

The internal ribosome entry site (IRES) from the picornavirus family has frequently been used to express multiple genes from a polycistronic message in retroviral vectors. While examining factors affecting levels of gene expression in IRES-containing retroviral vectors, it was found that retroviral vectors expressing the two genes linked by IRES, the reporter gene and the selectable marker neo, produced significantly lower levels of protein than those containing a reporter gene alone. This observation has been made with various cDNA sequences. However, when the neo was replaced with a different cDNA, the level of gene expression was increased, often to the level achieved with a vector expressing a single gene, suggesting that the bacterial neo sequence has a negative effect on expression. Analysis of the steady-state RNA levels isolated from transfected packaging cells showed that the neo-containing retroviral vectors produced significantly lower levels of RNA than those lacking this bacterial sequence indicating that neo interferes with expression of the neighboring gene at the level of RNA. Furthermore, the order of genes in the IRES-neo-containing vectors appeared to be more important than in the vector lacking the neo sequence. Our results suggest that neo has to be used in the retroviral vector with care, especially when a high level gene expression is needed.

Animals↗
PubMed1999

Intra-articular delivery of a herpes simplex virus IL-1Ra gene vector reduces inflammation in a rabbit model of arthritis.

To evaluate the use of HSV-based vectors for arthritis gene therapy we have constructed a first-generation, ICP4 deficient, replication defective herpes simplex virus (HSV) vector (S/0-) and a second-generation HSV vector derivative (T/0-) deficient for the immediate-early genes ICP4, 22 and 27, each carrying a soluble TNF receptor or IL-1 receptor antagonist transgene cassette. A rabbit synovial-fibroblast line in culture, infected by either vector enabled high-level expression of the transgene product. However, following a single intra-articular injection of the vectors into rabbit knee joints, only the second-generation, HSV T/0- vector expressed detectable levels of soluble TNFR in synovial fluid. Synovial lavage fluid from inoculated joints con- tained up to 12 ng/ml of soluble receptor that persisted at detectable, but reduced levels for at least 7 days. When tested in an experimental model of arthritis generated by intra-articular overexpression of interleukin-1beta using retrovirus transduced synovial cells, the HSV T/0- vector expressing the interleukin-1 receptor antagonist was found to inhibit leukocytosis and synovitis significantly. The improved levels and duration of intra-articular transgene expression achieved via HSV-mediated gene delivery suggest that an HSV vector system could be used for therapeutic applications in patients with rheumatoid arthritis (RA) and other joint-related inflammatory diseases.

Adoptive Transfer↗
PubMed1999

High efficiency in vitro gene transfer into vascular tissues using a pseudotyped retroviral vector without pseudotransduction.

Murine leukemia virus (MuLV)-derived retroviral vectors have had limited application in vascular gene therapy because of low transduction efficiency of vascular tissues, both in vitro and in vivo. In this study, we compared the gene transfer efficiency of two retroviral vectors: amphotropic MuLV and a MuLV vector pseudotyped with the vesicular stomatitis virus G glycoprotein (VSV-G) envelope. Target vascular tissues included human endothelial cells (EC), smooth muscle cells (SMC) and saphenous veins (SV). Transduction efficiency of human EC and SMC was significantly higher for VSV-G pseudotyped MuLV vector (90%) than for Amphotropic MuLV (20%). Luminal surface en face analysis of transduced cultured SV showed a six- to 10-fold greater transduction efficiency with VSV-G pseudotyped MuLV. The tissue plasminogen activator (tPA) gene was transduced into EC using each vector. Four days following transduction, a 12-fold higher tPA antigen concentration and a 38-fold higher tPA enzymatic activity was measured from cells transduced with the VSV-G pseudotyped vectors as compared with the amphotropic MuLV. There was no detectable pseudotransduction (protein transfer) associated with the VSV-G MuLV vector. Both AZT inhibition of reverse transcriptase and cell division arrest by gamma irradiation inhibited transduction, indicating that viral transduction correlated with RNA reverse transcription and cell proliferation. MuLV pseudotyped with the VSV-G envelope glycoprotein is an effective retroviral vector for vascular gene therapy.

Cell Division↗
PubMed2000

Effective repeat administration with adenovirus vectors to the muscle.

Effective repeat administration of adenovirus vectors following intranasal or intravenous delivery is hindered by a strong neutralizing antibody response to the vector. Intramuscular administration of adenovirus vectors elicited a neutralizing antibody response that peaked between 14 and 21 days after infection. However, effective repeat intramuscular administration of adenovirus vectors was not hindered by the presence of neutralizing antibodies in the serum. Surprisingly, beta-galactosidase expression in the skeletal muscle of immunized mice was equivalent to that observed in control mice. As expected, these serum neutralizing antibodies effectively blocked repeat administration of adenovirus vectors when delivered via the intravenous route. These results were observed in both C57BL/6 and Balb/c mice and thus do not appear to be strain specific. Successful repeat administration of adenovirus vectors to skeletal muscle has significant implications for the use of adenovirus vectors clinically and for increasing the safety and efficacy of adenovirus vector gene delivery.

Adenoviridae↗
PubMed2000

Insulation from viral transcriptional regulatory elements improves inducible transgene expression from adenovirus vectors in vitro and in vivo.

Recombinant adenoviruses (Ad) are attractive vectors for gene transfer in vitro and in vivo. However, the widely used E1-deleted vectors as well as newer generation vectors contain viral sequences, including transcriptional elements for viral gene expression. These viral regulatory elements can interfere with heterologous promoters used to drive transgene expression and may impair tissue-specific or inducible transgene expression. This study demonstrates that the activity of a metal-inducible promoter is affected by Ad sequences both upstream and downstream of the transgene cassette in both orientations. Interference with expression from the heterologous promoter was particularly strong by viral regulatory elements located within Ad sequences nucleotides 1-341. This region is present in all recombinant Ad vectors, including helper-dependent vectors. An insulator element derived from the chicken gamma-globin locus (HS-4) was employed to shield the inducible promoter from viral enhancers as tested after gene transfer with first-generation Ad vectors in vitro and in vivo. Optimal shielding was obtained when the transgene expression cassette was flanked on both sides by HS-4 elements, except for when the HS-4 element was placed in 3'-->5' orientation in front of the promoter. The insulators reduced basal expression to barely detectable levels in the non-induced stage, and allowed for induction factors of approximately 40 and approximately 230 in vitro and in vivo, respectively. Induction ratios from Ad vectors without insulators were approximately 40-fold lower in vitro and approximately 15-fold lower in vivo. This study proves the potential of insulators to improve inducible or tissue-specific gene expression from adenovirus vectors, which is important for studying gene functions as well as for gene therapy approaches. Furthermore, our data show that insulators exert enhancer-blocking effects in episomal DNA.

Adenoviridae↗
PubMed2000

Helper-dependent adenovirus vectors: their use as a gene delivery system to neurons.

Recombinant adenovirus vectors have provided a major advance in gene delivery systems for post-mitotic neurons. However, the use of these first generation vectors has been limited due to the onset of virally mediated effects on cellular function and viability. In the present study we have used primary cultures of cerebellar granule neurons to examine the efficacy and cytotoxic effects of a helper-dependent adenovirus vector (hdAd) in comparison with a first generation vector. Our results demonstrate that the hdAd system provides equally efficient infectivity with significantly reduced toxicity in comparison to first generation vectors. Neurons transduced with a high titre of a first generation vector exhibited a time-dependent shut down in global protein synthesis and impaired physiological function as demonstrated by a loss of glutamate receptor responsiveness. This was followed by an increase in the fraction of TUNEL-positive cells and a loss of neuronal survival. In contrast, hdAds could be used at titres that transduce >85% of neurons with little cytotoxic effect: cellular glutamate receptor responses and rates of protein synthesis were indistinguishable from uninfected controls. Furthermore, cell viability was not significantly affected for at least 7 days after infection. At excessive viral titres, however, infection with hdAd did cause moderate but significant changes in cell function and viability in primary neuronal cultures. Thus, while these vectors are remarkably improved over first generation vectors, these also have limitations with respect to viral effects on cellular function and viability. Gene Therapy (2000) 7, 1200-1209.

Adenoviridae↗
PubMed2000

Improved titers of HIV-based lentiviral vectors using the SRV-1 constitutive transport element.

The development of lentiviral vectors that use Rev-independent mechanisms of nuclear export for their genomic RNA could facilitate the construction of novel anti-HIV vectors. We have improved the titers of Rev-independent lentiviral vectors having the SRV-1 CTE by mutating the major splice donor and acceptor sites present in the vector and by relocalization of the CTE sequences adjacent to the HIV-1 3'LTR. These two modifications have additive beneficial effects on vector titers and packaging efficiency. Packaging these CTE+ vectors expressing marker genes with a Rev-dependent HIV-1 helper vector yields higher titers than are obtained using a Rev-dependent lentiviral vector.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Trans-complementation of vector replication versus Coxsackie-adenovirus-receptor overexpression to improve transgene expression in poorly permissive cancer cells.

Gene therapy of cancer requires high-level expression of therapeutic transgenes in the target cells. Poor gene transfer is an important limitation to adenovector-mediated cancer gene therapy. We investigated two fundamentally different approaches to improve transgene expression in poorly permissive cancer cells. First, overexpression of the adenovirus attachment receptor CAR to facilitate receptor-mediated adenovector (AdV) uptake into the target cells; second, co-infection of this vector together with traces of replication competent adenovirus (RCA) accidentally arising by back-recombination during large-scale vector preparation. Among eight gastrointestinal cancer cell lines, the colorectal cancer lines showed particularly poor vector-mediated transgene expression (down to 67-fold lower than in HeLa cells). Expression of the adenovirus receptors CAR, alpha(v)beta5- and alpha(v)beta3-integrin were highly variable between cell lines. AdV uptake was significantly associated with CAR levels on the cell surface, but not with those of the integrins. AdV-mediated CAR overexpression increased CAR density on the surface of all investigated tumor cells and led to enhancement of transgene expression by 1.8- to 6.7-fold. The other principle to enhance transgene expression was 'trans-complementation' of the therapeutic vector, ie induction of its replication within the target cells. Traces of RCA in a vector preparation, as well as purified RCA were found to provide sufficient E1-region transcripts to induce replication of the therapeutic vector genome. The number of adenovector-based transgene expression cassettes was greatly amplified by this principle, notably without any influence on the rate of vector entry. Co-infection of four colorectal cancer cell lines with marker vector plus RCA (at around 240:1 particle ratio) resulted in far stronger enhancement of transgene expression (up to 46-fold) as compared with CAR overexpression, even in cancers almost refractory to standard adenovector-mediated gene transfer. Whereas RCAs need to be strictly avoided in gene therapy of non-malignant diseases for safety reasons, the magnitude of helper virus-induced therapeutic transgene expression could possibly warrant application of this principle to overcome the resistance of highly malignant cancers against gene therapy.

Adenoviridae↗
PubMed2001

A simplified system for constructing recombinant adenoviral vectors containing heterologous peptides in the HI loop of their fiber knob.

The use of recombinant adenovirus (Ad) vectors containing genetically modified capsid proteins is an attractive strategy for achieving targeted gene transfer. The HI loop of the fiber knob is a promising candidate location for the incorporation of foreign ligands for achieving this goal. However, the method of constructing an Ad vector containing a foreign ligand in the HI loop of the fiber knob has proved difficult. In this study, we developed a simple system to construct fiber-modified vectors. To do this, a vector plasmid containing a complete E1/E3-deleted Ad type 5 genome and a unique Csp45I and/or ClaI site between positions 32679 and 32680 of the Ad genome (residues threonine-546 and proline-547 of the fiber protein) was constructed. Oligonucleotides corresponding to the Arg-Gly-Asp (RGD) or Asn-Gly-Arg (NGR)-containing peptide motif (as a model) and containing a Csp45I and/or ClaI recognition site, were ligated into the Csp45I and/or ClaI-digested plasmid. The foreign transgene expression cassette was inserted into the E1 deletion site of the vector plasmid and the fiber-mutant Ad vector was produced by transfection of the PacI-digested plasmid into 293 cells. The virus containing the RGD or NGR peptide on the fiber knob was able to infect human glioma cells, which do not express coxsackievirus and adenovirus receptor (CAR), one of the Ad virus receptors, about 100-1000 times more efficient than the virus containing wild-type fiber. This suggested that the mutant virus mediated CAR-independent cell entry pathway. The simplicity of this method allows not only for easy construction of fiber-mutant Ad vectors, but also for screening of the peptides that target the vector to the desired cells and tissues.

Adenoviridae↗