Dataset Information

AAV8-mediated hepatic gene transfer in infant rhesus monkeys (Macaca mulatta).

ABSTRACT: Many genetic metabolic diseases manifest in infancy, therefore, it is important to develop effective treatments that could be implemented at this time. Adeno-associated virus serotype 8 (AAV8) gene transfer has been studied in neonatal mouse, cat, and dog models and shown some efficacy with a single hepatic injection at birth. AAV8-mediated liver gene transfer has also generated sustained therapeutic effects in feline and canine models of lysosomal storage disorders. In these models, delaying the age of vector treatment increased gene transfer stability. The growth rate of infant nonhuman primates is more similar to the growth trajectory of humans, thus infant monkeys provide an excellent model to study AAV gene transfer efficiency, stability, and safety. In this study, we report for the first time that AAV8-mediated hepatic gene transfer in infant monkeys is safe and efficient but less stable when compared to adolescent animals. Infant monkeys administered AAV8 intravenously at 1 week postnatal age achieved up to 98% transduction of hepatocytes within 7 days of injection; however, there was significant dilution of genomes and loss of transgene expression 35 days postadministration. Delaying the injection to 1 month postnatal age did not improve stability of transduction but decreased the antibody response to AAV8 capsid.

SUBMITTER: Wang L

PROVIDER: S-EPMC3222523 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

AAV8-mediated hepatic gene transfer in infant rhesus monkeys (Macaca mulatta).

Wang Lili L Bell Peter P Lin Jianping J Calcedo Roberto R Tarantal Alice F AF Wilson James M JM

Molecular therapy : the journal of the American Society of Gene Therapy 20110802 11

Many genetic metabolic diseases manifest in infancy, therefore, it is important to develop effective treatments that could be implemented at this time. Adeno-associated virus serotype 8 (AAV8) gene transfer has been studied in neonatal mouse, cat, and dog models and shown some efficacy with a single hepatic injection at birth. AAV8-mediated liver gene transfer has also generated sustained therapeutic effects in feline and canine models of lysosomal storage disorders. In these models, delaying th ...[more]

PMID: 21811248

Similar Datasets

Project description:Infant temperament is theorized to lay the foundation for adult personality; however, many questions remain regarding personality in infancy, including the number of dimensions, extent to which they are adult-like, and their relation to other outcomes, such as mental and physical health. Here we tested whether adult-like personality dimensions are already present in infancy in a nonhuman primate species. We measured personality and subjective well-being in 7-month-old rhesus macaques (N = 55) using the Hominoid Personality Questionnaire and Subjective Well-Being Questionnaire, both of which were developed for adult primates based on human measures. Multiple human raters, who provided infants with daily care since birth, independently rated each infant. We found high interrater reliability. Results from a parallel analysis and scree plot indicated a five component structure, which, using principal components analysis, we found to be comprised of dimensions relating to Openness (e.g., curiosity, inquisitive, playfulness), Assertiveness (e.g., dominance, bullying, aggressive), Anxiety (e.g., vigilance, fearful), Friendliness (e.g., sociable, affectionate, sympathetic), and Intellect (e.g., organized, not erratic). These components are largely analogous to those in adult macaques, suggesting remarkably stable structural personality components across the lifespan. Infant macaques' subjective well-being positively correlates with Openness and Assertiveness and negatively correlated with Anxiety, similar to findings in adult macaques and other primates. Together, these findings suggest that, in macaques, infant personality dimensions may be conceptually related to adult personality and challenge the view that infant temperament may be disorganized and not as meaningful as adult personality. Further research is necessary to explore the antecedents, predictive validity, and stability of these personality components across situations and with development.

Project description:Studies examining hormones throughout pregnancy and lactation in women have been limited to single, or a few repeated, short-term measures of endocrine activity. Furthermore, potential differences in chronic hormonal changes across pregnancy/lactation between first-time and experienced mothers are not well understood, especially as they relate to infant development. Hormone concentrations in hair provide long-term assessments of hormone production, and studying these measures in non-human primates allows for repeated sampling under controlled conditions that are difficult to achieve in humans. We studied hormonal profiles in the hair of 26 female rhesus monkeys (Macaca mulatta, n=12 primiparous), to determine the influences of parity on chronic levels of cortisol (hair cortisol concentration, HCC) and progesterone (hair progesterone concentration, HPC) during early- to mid-pregnancy (PREG1), in late pregnancy/early lactation (PREG2/LACT1), and in peak lactation (LACT2). We also assessed infants' neurobehavioral development across the first month of life. After controlling for age and stage of pregnancy at the first hair sampling period, we found that HCCs overall peaked in PREG2/LACT1 (p=0.02), but only in primiparous monkeys (p<0.001). HPCs declined across pregnancy and lactation for all monkeys (p<0.01), and primiparous monkeys had higher HPCs overall than multiparous monkeys (p=0.02). Infants of primiparous mothers had lower sensorimotor reflex scores (p=0.02) and tended to be more irritable (p=0.05) and less consolable (p=0.08) in the first month of life. Moreover, across all subjects, HCCs in PREG2/LACT1 were positively correlated with irritability (r(s)=0.43, p=0.03) and negatively correlated with sensorimotor scores (r(s)=-0.41, p=0.04). Together, the present results indicate that primiparity influences both chronic maternal hormonal profiles and infant development. These effects may, in part, reflect differential reproductive and maternal effort in mothers with varied caretaking experience. In addition, infant exposure to relatively higher levels of maternal cortisol during the late fetal and early postnatal periods is predictive of poorer developmental outcomes.

Dataset Information

AAV8-mediated hepatic gene transfer in infant rhesus monkeys (Macaca mulatta).

Publications

AAV8-mediated hepatic gene transfer in infant rhesus monkeys (Macaca mulatta).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets