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Genetic counsellors hold unique positions in the health care field. Part of their role involves explaining genetic information to patients in a digestible way in order to empower them to make informed decisions about their genetic health. Medical interpreters are present during appointments with patients who have limited English proficiency (LEP). During these appointments, information is interpreted to the patient in their preferred language. Previous studies in the United States have explored the perspectives of genetic counsellors and interpreters in genetic counseling sessions with medical interpreters. There are currently no studies exploring these perspectives from a Canadian context. Additionally, there have been few studies exploring the point of view of the patients. Six genetic counsellors at the Health Sciences Center in Winnipeg, Manitoba and three patients with LEP were interviewed following genetic counselling appointments that required interpretation services. Semi-structured interviews were utilized to explore the participants’ perspectives, expectations, and experiences with medical interpretation. All interviews were transcribed and analyzed using thematic analysis to identify themes under a phenomenological framework. Five major themes were identified from our interviews: 1) Expectations of the providers, 2) Relationships and rapport building, 3) Mode of appointment delivery, 4) Flow of the genetic counselling session, and 5) Patients’ lived experiences. Overall, verbatim interpretation was preferred by all genetic counsellors and most patients. Additionally, genetic counsellors did not expect the medical interpreter to know genetic specific terminology and expressed that explaining these terms fell under their own domain and role. All participants preferred in-person to telephone appointments and pointed to visual cues as an important missing factor during phone appointments. Most genetic counsellors described having enough allocated time during

Genetic counsellors hold unique positions in the health care field. Part of their role involves explaining genetic information to patients in a digestible way in order to empower them to make informed decisions about their genetic health. Medical interpreters are present during appointments with patients who have limited English proficiency (LEP). During these appointments, information is interpreted to the patient in their preferred language. Previous studies in the United States have explored the perspectives of genetic counsellors and interpreters in genetic counseling sessions with medical interpreters. There are currently no studies exploring these perspectives from a Canadian context. Additionally, there have been few studies exploring the point of view of the patients. Six genetic counsellors at the Health Sciences Center in Winnipeg, Manitoba and three patients with LEP were interviewed following genetic counselling appointments that required interpretation services. Semi-structured interviews were utilized to explore the participants’ perspectives, expectations, and experiences with medical interpretation. All interviews were transcribed and analyzed using thematic analysis to identify themes under a phenomenological framework. Five major themes were identified from our interviews: 1) Expectations of the providers, 2) Relationships and rapport building, 3) Mode of appointment delivery, 4) Flow of the genetic counselling session, and 5) Patients’ lived experiences. Overall, verbatim interpretation was preferred by all genetic counsellors and most patients. Additionally, genetic counsellors did not expect the medical interpreter to know genetic specific terminology and expressed that explaining these terms fell under their own domain and role. All participants preferred in-person to telephone appointments and pointed to visual cues as an important missing factor during phone appointments. Most genetic counsellors described having enough allocated time during

Genetic counsellors hold unique positions in the health care field. Part of their role involves explaining genetic information to patients in a digestible way in order to empower them to make informed decisions about their genetic health. Medical interpreters are present during appointments with patients who have limited English proficiency (LEP). During these appointments, information is interpreted to the patient in their preferred language. Previous studies in the United States have explored the perspectives of genetic counsellors and interpreters in genetic counseling sessions with medical interpreters. There are currently no studies exploring these perspectives from a Canadian context. Additionally, there have been few studies exploring the point of view of the patients. Six genetic counsellors at the Health Sciences Center in Winnipeg, Manitoba and three patients with LEP were interviewed following genetic counselling appointments that required interpretation services. Semi-structured interviews were utilized to explore the participants’ perspectives, expectations, and experiences with medical interpretation. All interviews were transcribed and analyzed using thematic analysis to identify themes under a phenomenological framework. Five major themes were identified from our interviews: 1) Expectations of the providers, 2) Relationships and rapport building, 3) Mode of appointment delivery, 4) Flow of the genetic counselling session, and 5) Patients’ lived experiences. Overall, verbatim interpretation was preferred by all genetic counsellors and most patients. Additionally, genetic counsellors did not expect the medical interpreter to know genetic specific terminology and expressed that explaining these terms fell under their own domain and role. All participants preferred in-person to telephone appointments and pointed to visual cues as an important missing factor during phone appointments. Most genetic counsellors described having enough allocated time during

© 2016 The Royal Society of Chemistry. We report the synthesis, characterization, and assessment of a nanoparticle-based RNAi delivery platform that protects siRNA payloads against nuclease-induced degradation and efficiently delivers them to target cells. The nanocarrier is based on biodegradable mesoporous silicon nanoparticles (pSiNPs), where the voids of the nanoparticles are loaded with siRNA and the nanoparticles are encapsulated with graphene oxide nanosheets (GO-pSiNPs). The graphene oxide encapsulant delays release of the oligonucleotide payloads in vitro by a factor of 3. When conjugated to a targeting peptide derived from the rabies virus glycoprotein (RVG), the nanoparticles show 2-fold greater cellular uptake and gene silencing. Intravenous administration of the nanoparticles into brain-injured mice results in substantial accumulation specifically at the site of injury.

The original version of the Supplementary Information associated with this Article inadvertently omitted Supplementary Table 1. The HTML has now been updated to include a corrected version of the Supplementary Information.

Cerebrovascular changes occur in Alzheimer's disease (AD). Using in vivo phage display, we searched for molecular markers of the neurovascular unit, including endothelial cells and astrocytes, in mouse models of AD. We identified a cyclic peptide, CDAGRKQKC (DAG), that accumulates in the hippocampus of hAPP-J20 mice at different ages. Intravenously injected DAG peptide homes to neurovascular unit endothelial cells and to reactive astrocytes in mouse models of AD. We identified connective tissue growth factor (CTGF), a matricellular protein that is highly expressed in the brain of individuals with AD and in mouse models, as the target of the DAG peptide. We also showed that exogenously delivered DAG homes to the brain in mouse models of glioblastoma, traumatic brain injury, and Parkinson's disease. DAG may potentially be used as a tool to enhance delivery of therapeutics and imaging agents to sites of vascular changes and astrogliosis in diseases associated with neuroinflammation.

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries.

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury. The CAQK peptide selectively binds to injured mouse and human brain, and systemically injected CAQK specifically homes to sites of brain injury in mouse models. The CAQK target is a proteoglycan complex upregulated in brain injuries. Coupling to CAQK increased injury site accumulation of systemically administered molecules ranging from a drug-sized molecule to nanoparticles. CAQK-coated nanoparticles containing silencing oligonucleotides provided the first evidence of gene silencing in injured brain parenchyma by systemically administered siRNA. These findings present an effective targeting strategy for the delivery of therapeutics in clinical management of acute brain injuries., United States. Defense Advanced Research Projects Agency (Cooperative Agreement HR0011-13-2-0017)

Recent developments in multi-functional nanoparticles offer a great potential for targeted delivery of therapeutic compounds and imaging contrast agents to specific cell types, in turn, enhancing therapeutic effect and minimizing side effects. Despite the promise, site specific delivery carriers have not been translated into clinical reality. In this study, we have developed long circulating liposomes with the outer surface decorated with thioated oligonucleotide aptamer (thioaptamer) against E-selectin (ESTA) and evaluated the targeting efficacy and PK parameters. In vitro targeting studies using Human Umbilical Cord Vein Endothelial Cell (HUVEC) demonstrated efficient and rapid uptake of the ESTA conjugated liposomes (ESTA-lip). In vivo, the intravenous administration of ESTA-lip resulted in their accumulation at the tumor vasculature of breast tumor xenografts without shortening the circulation half-life. The study presented here represents an exemplary use of thioaptamer and liposome and opens the door to testing various combinations of thioaptamer and nanocarriers that can be constructed to target multiple cancer types and tumor components for delivery of both therapeutics and imaging agent.

Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA) against E-selectin (ESTA-1) by employing a two-step selection strategy: a recombinant protein-based TA binding selection from a combinatorial library followed by a cell-based TA binding selection using E-selectin expressing human microvascular endothelial cells. ESTA-1 selectively bound to E-selectin with nanomolar binding affinity (K(D) = 47 nM) while exhibiting minimal cross reactivity to P- and L-selectin. Furthermore, ESTA-1 binding to E-selectin on the endothelial cells markedly antagonized the adhesion (over 75% inhibition) of sLe(x) positive HL-60 cells at nanomolar concentration. ESTA-1 also bound specifically to the inflamed tumor-associated vasculature of human carcinomas derived from breast, ovarian, and skin but not to normal organs, and this binding was highly associated with the E-selectin expression level. Similarly, intravenously injected ESTA-1 demonstrated distinct binding to the tumor vasculature in a breast cancer xenograft model. Together, our data substantiates the discovery of a thioaptamer (ESTA-1) that binds to E-selectin with high affinity and specificity, thereby highlighting the potential application of ESTA-1 for E-selectin targeted delivery.