We are developing a number of strategies for monitoring gene therapy. The first approach is to monitor the specific phenotype of the genetic disease. For example, in mucopolysaccharidosis type VII (MPS VII) the genetic defect is failure to produce -glucuronidase. We are synthesizing glucuronides of fluorinated phenols. When the glycosidic bond is cleaved by -glucuronidase , the 19F chemical shift of the liberated phenol is expected to change by about 10ppm; furthermore, since the liberated fragment is anionic, it is expected to be trapped in the cell. In cystic fibrosis the genetic defect is in the chloride transporter (CFTR). This is known to result in an increase in the sodium and chloride concentrations in air passage fluids. We, therefore, are developing multiple quantum 23Na methods to detect and quantitate this alteration in sodium concentration. In hypercholesteremia the genetic defect is the lack of LDL receptors. We are developing methods to label LDL mole cules with magnetite so that delivery of LDL to liver lysosomes could be detected by MRI. These examples demonstrate how magnetic resonance methods can be developed to monitor genetic defects in enzymes, ion transport and receptors. However, we recognize that development of methods to monitor phenotypes of genetic defects will required an immense amount of effort and will not be completely reliable since similar genotypes may be expressed as different phenotypes or may be expressed to different extents. A more general approach is to develop a suitable marker gene that could be attached to the transfection vector and expressed by the same promotor. An ideal marker for MRI detection would be magnetite, which increases the relaxivity of water, which is 110 M in protons. Magnetite also has about a thousandfold higher relaxivity than an equivalent amount of iron (such as if found in the iron core of ferritin). Certain bacteria have the unique ability to produce magnetite from iron. T he protein responsible for this activity has been cloned and expressed in both bacterial and mammalian cells. We are exploring the utility of this protein as a marker for gene therapy.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
United States
Zip Code
Pang, Henry; Bow, Cora; Cheung, Jason Pui Yin et al. (2018) The UTE Disc Sign on MRI: A Novel Imaging Biomarker Associated With Degenerative Spine Changes, Low Back Pain, and Disability. Spine (Phila Pa 1976) 43:503-511
Ferraro, Pilar M; Jester, Charles; Olm, Christopher A et al. (2018) Perfusion alterations converge with patterns of pathological spread in transactive response DNA-binding protein 43 proteinopathies. Neurobiol Aging 68:85-92
Ercan, Altan; Kohrt, Wendy M; Cui, Jing et al. (2017) Estrogens regulate glycosylation of IgG in women and men. JCI Insight 2:e89703
Xie, Long; Dolui, Sudipto; Das, Sandhitsu R et al. (2016) A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment. Neuroimage Clin 11:388-397
Yadav, Santosh K; Kathiresan, Nagarajan; Mohan, Suyash et al. (2016) Gender-based analysis of cortical thickness and structural connectivity in Parkinson's disease. J Neurol 263:2308-2318
Finkelstein, Joel S; Lee, Hang; Leder, Benjamin Z et al. (2016) Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. J Clin Invest 126:1114-25
Rosenbaum, Michael; Leibel, Rudolph L (2016) Models of energy homeostasis in response to maintenance of reduced body weight. Obesity (Silver Spring) 24:1620-9
Machida, Manabu; Panasyuk, George Y; Wang, Zheng-Min et al. (2016) Radiative transport and optical tomography with large datasets. J Opt Soc Am A Opt Image Sci Vis 33:551-8
Ban, H Y; Schweiger, M; Kavuri, V C et al. (2016) Heterodyne frequency-domain multispectral diffuse optical tomography of breast cancer in the parallel-plane transmission geometry. Med Phys 43:4383
McCarthy, Ann L; Winters, Madeline E; Busch, David R et al. (2015) Scoring system for periventricular leukomalacia in infants with congenital heart disease. Pediatr Res 78:304-9

Showing the most recent 10 out of 414 publications