Whole-genome-scale identification of novel non-protein-coding RNAs controlling cell proliferation and survival through a functional forward genetics strategy.

Identification of cell fate-controlling lncRNAs is essential to our understanding of molecular cell biology. Here we present a human genome-scale forward-genetics approach for the identification of lncRNAs based on gene function. This approach can identify genes that play a causal role, and immediately distinguish them from those that are differentially expressed but do not affect cell function. Our genome-scale library plus next-generation-sequencing and bioinformatic approach, radically upscales the breadth and rate of functional ncRNA discovery. Human gDNA was digested to produce a lentiviral expression library containing inserts in both sense and anti-sense orientation. The library was used to transduce human Jurkat T-leukaemic cells. Cell populations were selected using continuous culture ± anti-FAS IgM, and sequencing used to identify sequences controlling cell proliferation. This strategy resulted in the identification of thousands of new sequences based solely on their function including many ncRNAs previously identified as being able to modulate cell survival or to act as key cancer regulators such as AC084816.1*, AC097103.2, AC087473.1, CASC15*, DLEU1*, ENTPD1-AS1*, HULC*, MIRLET7BHG*, PCAT-1, SChLAP1, and TP53TG1. Independent validation confirmed 4 out of 5 sequences that were identified by this strategy, conferred a striking resistance to anti-FAS IgM-induced apoptosis.

The Perilampidae of the United Arab Emirates and Yemen (Hymenoptera: Chalcidoidea).

The family Perilampidae is reported for the first time from the Arabian Peninsula. Krombeinius almokha Darling n. sp. is described from Yemen and seven species of Perilampus Latreille are recorded and illustrated from Yemen and the United Arab Emirates. Two species are recognized in the P. auratus group, Perilampus ardens Yoo Darling n. sp., P. awbalus Yoo Darling n. sp., one species in the P. laevifrons/chrysopae group, Perilampus khor Yoo Darling n. sp., three species in the P. tristis group, Perilampus rainerius (Argaman), 1990, P. houbaraensis Yoo Darling n. sp., P. yemenensis n. sp., and Perilampus microgastris Ferrire, 1930. The species show primarily Afrotropical and Palaearctic affinities. Comparisons and images are also provided for five extralimital species, P. auratus Panzer, 1798, P. tristis Mayr, 1905, P. chrysonotus Frster, 1859, P. seyrigi Risbec, 1952, and P. noemi Nikolskaya, 1952, and a lectotype is designated for P. microgastris (present designation). The biogeographic affinities of the Arabian Peninsula Perilampidae are discussed as is dwarfism in desert Hymenoptera.

Autophagy supports generation of cells with high CD44 expression via modulation of oxidative stress and Parkin-mediated mitochondrial clearance.

High CD44 expression is associated with enhanced malignant potential in esophageal squamous cell carcinoma (ESCC), among the deadliest of all human carcinomas. Although alterations in autophagy and CD44 expression are associated with poor patient outcomes in various cancer types, the relationship between autophagy and cells with high CD44 expression remains incompletely understood. In transformed oesophageal keratinocytes, CD44Low-CD24High (CD44L) cells give rise to CD44High-CD24-/Low (CD44H) cells via epithelial-mesenchymal transition (EMT) in response to transforming growth factor (TGF)-ß. We couple patient samples and xenotransplantation studies with this tractable in vitro system of CD44L to CD44H cell conversion to investigate the functional role of autophagy in generation of cells with high CD44 expression. We report that high expression of the autophagy marker cleaved LC3 expression correlates with poor clinical outcome in ESCC. In ESCC xenograft tumours, pharmacological autophagy inhibition with chloroquine derivatives depletes cells with high CD44 expression while promoting oxidative stress. Autophagic flux impairment during EMT-mediated CD44L to CD44H cell conversion in vitro induces mitochondrial dysfunction, oxidative stress and cell death. During CD44H cell generation, transformed keratinocytes display evidence of mitophagy, including mitochondrial fragmentation, decreased mitochondrial content and mitochondrial translocation of Parkin, essential in mitophagy. RNA interference-mediated Parkin depletion attenuates CD44H cell generation. These data suggest that autophagy facilitates EMT-mediated CD44H generation via modulation of redox homeostasis and Parkin-dependent mitochondrial clearance. This is the first report to implicate mitophagy in regulation of tumour cells with high CD44 expression, representing a potential novel therapeutic avenue in cancers where EMT and CD44H cells have been implicated, including ESCC.

ZEB1 and TCF4 reciprocally modulate their transcriptional activities to regulate Wnt target gene expression.

The canonical Wnt pathway (TCF4/ß-catenin) has important roles during normal differentiation and in disease. Some Wnt functions depend on signaling gradients requiring the pathway to be tightly regulated. A key Wnt target is the transcription factor ZEB1 whose expression by cancer cells promotes tumor invasiveness by repressing the expression of epithelial specification markers and activating mesenchymal genes, including a number of Wnt targets such as LAMC2 and uPA. The ability of ZEB1 to activate/repress its target genes depends on its recruitment of corepressors (CtBP, BRG1) or coactivators (p300) although conditions under which ZEB1 binds these cofactors are not elucidated. Here, we show that TCF4 and ZEB1 reciprocally modulate each other's transcriptional activity: ZEB1 enhances TCF4/ß-catenin-mediated transcription and, in turn, Wnt signaling switches ZEB1 from a repressor into an activator. In colorectal cancer (CRC) cells with active Wnt signaling, ZEB1 enhances transcriptional activation of LAMC2 and uPA by TCF4/ß-catenin. However, in CRC cells with inactive Wnt, ZEB1 represses both genes. Reciprocal modulation of ZEB1 and TCF4 activities involves their binding to DNA and mutual interaction. Wnt signaling turns ZEB1 into an activator by replacing binding of CtBP/BRG1 in favor of p300. Using a mouse model of Wnt-induced intestinal tumorigenesis, we found that downregulation of ZEB1 reduces the expression of LAMC2 in vivo. These results identify a mechanism through which Wnt and ZEB1 transcriptional activities are modulated, offering new approaches in cancer therapy.

Lentivirus-induced 'Smart' dendritic cells: Pharmacodynamics and GMP-compliant production for immunotherapy against TRP2-positive melanoma.

Monocyte-derived conventional dendritic cells (ConvDCs) loaded with melanoma antigens showed modest responses in clinical trials. Efficacy studies were hampered by difficulties in ConvDC manufacturing and low potency. Overcoming these issues, we demonstrated higher potency of lentiviral vector (LV)-programmed DCs. Monocytes were directly induced to self-differentiate into DCs (SmartDC-TRP2) upon transduction with a tricistronic LV encoding for cytokines (granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4)) and a melanoma antigen (tyrosinase-related protein 2 (TRP2)). Here, SmartDC-TRP2 generated with monocytes from five advanced melanoma patients were tested in autologous DC:T cell stimulation assays, validating the activation of functional TRP2-specific cytotoxic T lymphocytes (CTLs) for all patients. We described methods compliant to good manufacturing practices (GMP) to produce LV and SmartDC-TRP2. Feasibility of monocyte transduction in a bag system and cryopreservation following a 24-h standard operating procedure were achieved. After thawing, 50% of the initial monocyte input was recovered and SmartDC-TRP2 self-differentiated in vitro, showing uniform expression of DC markers, detectable LV copies and a polyclonal LV integration pattern not biased to oncogenic loci. GMP-grade SmartDC-TRP2 expanded TRP2-specific autologous CTLs in vitro. These results demonstrated a simpler GMP-compliant method of manufacturing an effective individualized DC vaccine. Such DC vaccine, when in combination with checkpoint inhibition therapies, might provide higher specificity against melanoma.

Optimised concentration and purification of retroviruses using membrane chromatography.

The ability of an anion exchange membrane to purify a γ-retrovirus was assessed and optimised with respect to different loading and wash buffers. Recoveries of infectious virus greater than 50% were consistently obtained, while specific titre was increased up to one thousand fold when compared to the material loaded. Specific proteins removed and retained by this optimised process were identified by mass spectrometry. It was possible to successfully bind and elute the equivalent of 1.27 × 10(8) Ifu/ml of ion exchange membrane. This could then be highly concentrated, with infectious virus concentrated to a maximum of 420-fold compared to the load.

Not looking where you are leaping: a novel method of oriented travel in the caterpillar Calindoea trifascialis (Moore) (Lepidoptera: Thyrididae).

The prepupation caterpillar of the Southeast Asian moth Calindoea trifascialis constructs a leaf shelter that jumps across the ground using a jumping method novel among the insects. We found that movement path direction was correlated to the direction opposite to the most intense light. Correlated random walk (CRW) analyses found net squared displacements higher than predicted by a CRW, and fractal dimension analysis indicated straighter paths at large spatial scales. Rearing experiments showed high mortality from predation on the ground, but higher mortality resulted from sun exposure. We interpret jumping path orientation as an efficient search strategy to find shade in a variable landscape, given limited perception, in the presence of overheating and desiccation risks.

Human liver regeneration is characterized by the coordinated expression of distinct microRNA governing cell cycle fate.

In the absence of adequate compensatory regeneration, overwhelming liver damage can cause acute liver failure (ALF) and death without emergent liver transplantation (LT). Auxiliary LT produces satisfactory outcomes in this setting, with the prospect of native liver regeneration sustaining long-term survival. Since animal models only partially recapitulate human liver regeneration, we investigated the molecular mechanisms controlling it in this unique LT setting, as an exemplar of human liver regeneration. We demonstrate coordinated changes in expression of microRNA (miRNA) during regeneration that drive proliferation, innate immunity and angiogenesis. In contrast, failed regeneration in a similar cohort is associated with distinct miRNA enforcing cell cycle inhibition and DNA methylation. The miRNA expression associated with successful or failed regeneration when recapitulated in vitro, triggered expression of cardinal regeneration-linked genes promoting cell cycle entry or inhibition, respectively. Furthermore, inhibition of miRNA 150, 663 and 503, whose downregulation is associated with successful regeneration, induced cell proliferation which a key determinant of successful regeneration. Our data indicate that human liver regeneration may be orchestrated by distinct miRNA controlling key regeneration-linked processes including hepatocyte proliferation. To our knowledge this is the first characterization of molecular processes associated with human liver regeneration.

A phylogenetic analysis of the megadiverse Chalcidoidea (Hymenoptera).

Chalcidoidea (Hymenoptera) is extremely diverse with an estimated 500 000 species. We present the first phylogenetic analysis of the superfamily based on both morphological and molecular data. A web-based, systematics workbench mx was used to score 945 character states illustrated by 648 figures for 233 morphological characters for a total of 66 645 observations for 300 taxa. The matrix covers 22 chalcidoid families recognized herein and includes 268 genera within 78 of 83 subfamilies. Morphological data were analysed alone and in combination with molecular data from ribosomal 18S (2105 bp) and 28S D2-D5 expansion regions (1812 bp). Analyses were analysed alone and in combined datasets using implied-weights parsimony and likelihood. Proposed changes in higher classification resulting from the analyses include: (i) recognition of Eriaporidae, revised status; (ii) recognition of Cynipencyrtidae, revised status; (iii) recognition of Azotidae, revised status; (iv) inclusion of Sycophaginae in Agaonidae, revised status; (v) reclassification of Aphelinidae to include Aphelininae, Calesinae, Coccophaginae, Eretmocerinae and Eriaphytinae; (vi) inclusion of Cratominae and Panstenoninae within Pteromalinae (Pteromalidae), new synonymy; (vii) inclusion of Epichrysomallinae in Pteromalidae, revised status. At a higher level, Chalcidoidea was monophyletic, with Mymaridae the sister group of Rotoitidae plus the remaining Chalcidoidea. A eulophid lineage was recovered that included Aphelinidae, Azotidae, Eulophidae, Signiphoridae, Tetracampidae and Trichogrammatidae. Eucharitidae and Perilampidae were monophyletic if Eutrichosomatinae (Pteromalidae) was included, and Eupelmidae was monophyletic if Oodera (Pteromalidae: Cleonyminae) was included. Likelihood recovered a clade of Eupelmidae + (Tanaostigmatidae + (Cynipencyrtus + Encyrtidae). Support for other lineages and their impact on the classification of Chalcidoidea is discussed. Several life-history traits are mapped onto the new phylogeny.

Missed opportunities for identifying primary HIV within genitourinary medical/HIV services.

To assess the ability of three genitourinary medical centres to clinically identify primary HIV infection (PHI). Cases of recently acquired HIV infection, identified using the Health Protection Agency (HPA) avidity assay on all HIV diagnoses from January to August 2009, were investigated by case-note review. Sixty-four individuals were identified as PHI using the HPA avidity assay. Of 64 individuals, 31 (48%) were identified clinically. Imperial College identified 8/26 (31%), Guys and St Thomas' 15/27 (56%) and Brighton 8/11 (73%). Clinical suspicion of PHI was associated with reported unprotected anal intercourse (P = 0.017), seroconversion symptoms (P = 0.0004), a negative HIV test within six months (P = 0.024) and avidity assay result availability (P = 0.0169). Seventy percent of PHI cases missed had a documented risk factor. Thirty-five percent of those clinically identified with PHI were documented as informed of the associated enhanced infectivity. Suspicion of PHI was low despite documented risk factors and recent HIV-negative antibody tests. Counselling to prevent onward transmission was suboptimal.

Lentivirus capture directly from cell culture with Q-functionalised microcapillary film chromatography.

A new disposable adsorbent material for fast anion-exchange capture of nano-complexes without prefiltering, clarification or pre-processing of samples was developed based on plastic microcapillary films (MCFs). An MCF containing 19 parallel microcapillaries, each with a mean internal diameter of 142 ± 10 µm, was prepared using a melt extrusion process from an ethylene-vinyl alcohol copolymer (EVOH). The MCF internal surfaces were functionalised using branched chain chemistries to attach quaternary amine groups producing an anion-exchange adsorbent. The purification of nano-complexes using this newly fabricated MCF-EVOH-Q was successfully demonstrated with the capture of lentivirus from pre-filtered culture harvest. This 5m chromatographic substrate was found to bind and elute ∼40% of bound lentivirus or 2.5 × 10(6)infectious units (ifu). The unique properties of this chromatographic substrate that allow the passage of large particulates was further demonstrated with the capture of lentiviral particles from unfiltered un-processed culture media containing cells and cell debris. Using this approach, 56% or 1 × 10(7)ifu of captured lentivirus was eluted. A device based on this new material might be used at an early stage in clinical lentiviral production to harvest lentiviral particles, directly from bioreactors.

Parotid secretory protein binds phosphatidylinositol (3,4) bisphosphate.

Molecular interactions that direct trafficking of secreted proteins are not well-described in salivary glands. Here, we report that the soluble cargo protein Parotid Secretory Protein (PSP) is bound to the membranes of secretory granules isolated from rat parotids. This is apparently due to specific interaction with phosphatidylinositol phosphates (PtdInsP). PSP binds PtdIns(3,4)P(2), 10-fold greater than PtdIns(3,5)P(2) or PtdIns(4)P, and does not bind PtdIns(3)P or PtdIns(5)P. Human PSP synthesized in vitro also binds PtdIns(3,4)P(2). Bacterially expressed rat PSP binds PtdIns(3,4)P(2) with a K(d) of 2.4 x 10(-11) M. Other major secretory proteins (amylase, proline-rich protein) are not bound to isolated granule membranes and do not bind phosphatidylinositol phosphates. Immunofluorescence shows PtdIns(3,4)P(2) at the secretory granules, and fluorescent PtdIns(3,4)P(2) can flip from the outer leaflet to the inner leaflet of the membrane. Binding of PSP to PtdInsPs may contribute to sorting during the formation of the secretory granules, or sorting by retention during maturation of the granules.

Immobilized metal affinity chromatography of histidine-tagged lentiviral vectors using monolithic adsorbents.

Histidine-tagged lentiviral vectors were separated from crude cell culture supernatant using labscale monolithic adsorbents by immobilized metal affinity chromatography. The capture capacity, concentration factor, purification factor, and elution efficiency of a supermacroporous cryogel monolith were evaluated against the BIA Separations convective interaction media (CIM) disc, which is a commercial macroporous monolith. The morphology of the polymeric cryogel material was characterised by scanning electron microscopy. Iminodiacetic acid was used as the metal chelating ligand in both monoliths and the chelating capacity for metal ions was found to be comparable. The CIM-IDA-Ni(2+) adsorbent had the greatest capture capacity (6.7 x 10(8) IU/ml of adsorbent), concentration factor (1.3-fold), and elution efficiency (69%). Advantages of the cryogel monoliths included rapid, low pressure processing as well low levels of protein and DNA in the final purified vector preparations.

Parotid secretory granules: crossroads of secretory pathways and protein storage.

Saliva plays an important role in digestion, host defense, and lubrication. The parotid gland contributes a variety of secretory proteins-including amylase, proline-rich proteins, and parotid secretory protein (PSP)-to these functions. The regulated secretion of salivary proteins ensures the availability of the correct mix of salivary proteins when needed. In addition, the major salivary glands are targets for gene therapy protocols aimed at targeting therapeutic proteins either to the oral cavity or to circulation. To be successful, such protocols must be based on a solid understanding of protein trafficking in salivary gland cells. In this paper, model systems available to study the secretion of salivary proteins are reviewed. Parotid secretory proteins are stored in large dense-core secretory granules that undergo stimulated secretion in response to extracellular stimulation. Secretory proteins that are not stored in large secretory granules are secreted by either the minor regulated secretory pathway, constitutive secretory pathways (apical or basolateral), or the constitutive-like secretory pathway. It is proposed that the maturing secretory granules act as a distribution center for secretory proteins in salivary acinar cells. Protein distribution or sorting is thought to involve their selective retention during secretory granule maturation. Unlike regulated secretory proteins in other cell types, salivary proteins do not exhibit calcium-induced aggregation. Instead, sulfated proteoglycans play a role in the storage of secretory proteins in parotid acinar cells. This work suggests that unique sorting and retention mechanisms are responsible for the distribution of secretory proteins to different secretory pathways from the maturing secretory granules in parotid acinar cells.

Influence of interleukin-4 on the phenotype and function of bone marrow-derived murine dendritic cells generated under serum-free conditions.

Murine bone marrow-derived dendritic cells (DC) can be generated by culture in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF) alone or GM-CSF in conjunction with interleukin-4 (IL-4). However, these two culture methods result in the production of heterogeneous DC populations with distinct phenotypic and stimulatory properties. In this study, we investigated the properties of DC generated under serum-free conditions in the presence or absence of IL-4 and compared their yield and phenotype to that of DC generated in the presence of fetal calf serum (FCS) (+/-IL-4). We did not observe a significant difference in the total cell yield between these four culture conditions, although the proportion of CD11c+ DC in cultures that received FCS was higher than that of their counterparts generated under serum-free conditions. Also, the four culture conditions generated CD11c+ DC with comparable levels of major histocompatibility complex (MHC) class II, CD40, CD80 and CD86 expression, with the exception of cells cultured under serum-free conditions in the absence of IL-4, which displayed suboptimal levels of these markers. Moreover, we compared the functional and stimulatory properties of DC generated under serum-free conditions in the presence or absence of IL-4. DC cultured in the presence of IL-4 were stronger stimulators of allogeneic splenocytes in a primary mixed lymphocyte reaction (MLR) and of naive antigen-specific OT-II transgenic T cells when pulsed with the class II ovalbumin (OVA)323-339 peptide or whole OVA protein than DC cultured in the absence of IL-4. However, both DC populations displayed a similar capacity to take up fluorescein isothiocyanate (FITC)-albumin by macropinocytosis and FITC-Dextran by the mannose receptor and to secrete IL-12 in response to stimulation with lipopolysaccharide (LPS) or an agonistic anti-CD40 monoclonal antibody. Therefore, we conclude that although both DC culture methods result in the production of DC with similar functional abilities, under serum-free conditions, DC cultured in GM-CSF and IL-4 show an increased stimulatory potential over DC cultured in GM-CSF alone. This is an important consideration in the design of experiments where DC are being exploited as immunotherapeutic vaccines.

Developmental and functional evidence of a role for Zfhep in neural cell development.

The rat Zfhep gene encodes a member of the Zfh family of transcription factors having a homeodomain-like sequence and multiple zinc fingers. We examined expression of Zfhep in the rat forebrain during embryonic and postnatal development. Zfhep mRNA was strongly expressed in the progenitor cells of the ventricular zone around the lateral ventricles on E14 and E16, but showed little expression in cells that had migrated to form the developing cortex. Dual labeling with PCNA demonstrated expression of Zfhep mRNA in proliferating cells. Expression of Zfhep in the ventricular zone decreases during late development as the population of progenitor cells decreases. This pattern is distinctly different from other members of the Zfh family. We also examined the expression of Zfhep protein during retinoic acid-induced neurogenesis of P19 embryonal carcinoma cells. Zfhep is highly expressed in P19 neuroblasts, and expression decreases by the time of morphological neurogenesis. Hence, both P19 cells and embryonic brain demonstrate a loss of Zfhep expression during the transition from proliferating precursor to differentiated neural cells. We investigated a possible link between Zfhep and proliferation by treating human glial cell lines with Zfhep antisense phosphorothioate oligodeoxynucleotides. Two Zfhep antisense oligonucleotides repressed proliferation of either U-138 or U-343 glioblastoma cells more than control oligonucleotides. Based on the expression patterns of Zfhep in vivo and in the P19 cell model of neurogenesis, we suggest that Zfhep may play a role in proliferation or differentiation of neural cells.

Production of a cyanogenic secretion by a thyridid caterpillar (Calindoea trifascialis, Thyrididae, Lepidoptera).

The thyridid caterpillar, Calindoea trifascialis, when disturbed, emits a defensive secretion from two sac-like glands that open dorsolaterally on the first abdominal segment. The larva has two arm-like protuberances that project outward from the body just in front of the gland openings. These "arms", which are wetted by secretion when the larva activates its glands, appear to function specifically for administration of the fluid. A primary component of the secretion in mandelonitrile, a cyanogenic compound, but the fluid also contains other potential deterrents, including benzaldehyde, benzoic acid, (E,E)-alpha-farnesene, and 3-methylbutyl-3-methylbutanoate. Tests done in the field in Vietnam, where the species is native, showed the secretion to be protective against ants.

T3-activation of the rat growth hormone gene is inhibited by a zinc finger/homeodomain protein.

Since the transcription factor Zfhep is expressed in somatotropes and binds the rat growth hormone (rGH) gene T3-response element (TRE), we investigated whether Zfhep regulates the response of this gene to T3. In cotransfection experiments, Zfhep did not regulate the native rGH promoter in the absence of T3. However, Zfhep repressed T3-mediated activation significantly in either GH(3) or JEG-3 cells. Up to 70% repression was mediated through the rGH TRE in a heterologous promoter (thymidine kinase), but was not observed with the idealized DR4 or chicken lysozyme F2 TREs. Zfhep apparently does not repress T3-mediated activation simply by competition for binding to DNA since the C-terminal DNA-binding domain of Zfhep (which is sufficient for DNA-binding) is not sufficient for repression and since cotransfection of excess thyroid hormone receptor (TR) did not prevent repression by Zfhep. These data indicate that the rGH TRE is a composite element that can integrate Zfhep and T3 regulation.

Protein transduction: an alternative to genetic intervention?

Protein transduction, an emerging technology with potential applications in gene therapy, can best be described as the internalisation of proteins into the cell, from the external environment. This process relies on the inherent property of a small number of proteins and peptides of being able to penetrate the cell membrane. The transducing property of these molecules can be conferred upon proteins which are expressed as fusions with them and thus offers an alternative to gene therapy for the delivery of therapeutic proteins into target cells. This review describes the three most commonly used protein transduction vehicles; the antennapedia peptide, the herpes simplex virus VP22 protein and HIV TAT protein transduction domain. The future prospects for the application of this technology in gene therapy are also discussed.

Streptavidin paramagnetic particles provide a choice of three affinity-based capture and magnetic concentration strategies for retroviral vectors.

Three strategies have been designed to concentrate infectious retroviral vectors from the supernatants of human- (HT1080) and murine- (NIH 3T3) based packaging cells. Streptavidin-conjugated paramagnetic particles in conjunction with (i) antibodies directed against murine fibronectin, (ii) biotinylated lectins, or (iii) biotin-modified packaging cell-surface proteins allow affinity-mediated magnetic concentration of retroviral vectors. Retroviral titers (assayed by colony formation of human myeloid K562 cells) are increased by 1-4 x 10(3)-fold after volume reductions of only 125-fold. Using these procedures, preparations of 5 x 10(8) cfu/ml are routinely made from relatively low-titer (2-5 x 10(5) cfu/ml) starting material. High-titer (paramagnetic) retroviral vector preparations can be used for magnetic field-dependent retroviral infection in vitro. Magnetic field-dependent localization such as this may enable the in vivo administration of formulations that concentrate retroviral infection to the required target tissues and organs.