Browsing by Author "Xie, Jun"

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    Coagulation factor IX gene transfer to non-human primates using engineered AAV3 capsid and hepatic optimized expression cassette
    (Elsevier, 2021-08-26) Kumar, Sandeep R. P.; Xie, Jun; Hu, Shilang; Ko, Jihye; Huang, Qifeng; Brown, Harrison C.; Srivastava, Alok; Markusic, David M.; Doering, Christopher B.; Spencer, H. Trent; Srivastava, Arun; Gao, Guangping; Herzog, Roland W.; Pediatrics, School of Medicine
    Hepatic gene transfer with adeno-associated viral (AAV) vectors shows much promise for the treatment of the X-linked bleeding disorder hemophilia B in multiple clinical trials. In an effort to further innovate this approach and to introduce alternative vector designs with potentially superior features into clinical development, we recently built a vector platform based on AAV serotype 3 because of its superior tropism for human hepatocytes. A vector genome with serotype-matched inverted terminal repeats expressing hyperactive human coagulation factor IX (FIX)-Padua was designed for clinical use that is optimized for translation using hepatocyte-specific codon-usage bias and is depleted of immune stimulatory CpG motifs. Here, this vector genome was packaged into AAV3 (T492V + S663V) capsid for hepatic gene transfer in non-human primates. FIX activity within or near the normal range was obtained at a low vector dose of 5 × 1011 vector genomes/kg. Pre-existing neutralizing antibodies, however, completely or partially blocked hepatic gene transfer at that dose. No CD8+ T cell response against capsid was observed. Antibodies against the human FIX transgene product formed at a 10-fold higher vector dose, albeit hepatic gene transfer was remarkably consistent, and sustained FIX activity in the normal range was nonetheless achieved in two of three animals for the 3-month duration of the study. These results support the use of this vector at low vector doses for gene therapy of hemophilia B in humans.
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    Posterior sub-Tenon capsule anesthesia for photocoagulation treatment of diabetic retinopathy performed in an inner-city county hospital clinic setting
    (Office of the Vice Chancellor for Research, 2015-04-17) Wise, Ryan J.; Pattar, Guruprasad R.; Xie, Jun; Phan, Anh-Danh T.
    Proliferative diabetic retinopathy (PDR) is a blinding eye disease demanding prompt therapy. However, treatment with panretinal photocoagulation (PRP) can be painful thereby limiting its extent. In addition, compliance to diabetic eye visits remains poor particularly in inner cities. Therefore, it is imperative to optimize treatment during clinic visits. The purpose of this study is to present the effect of sub-Tenon (Sub-T) capsule lidocaine anesthesia on PRP treatment extent for PDR performed during the eye clinic visit. This is an IRB-approved retrospective review of initial 12 eyes (9 subjects) with PDR undergoing PRP treatment involving Sub-T anesthesia in the eye clinic. Sub-T capsule lidocaine anesthesia was delivered and PRP was immediately performed. Primary end point was extent of treatment (number of PRP laser spots) delivered. Comparison was made to PRP in prior sessions without Sub-T anesthesia. All subjects had active PDR and sometimes vitreous hemorrhage (VH) at time of treatment. Decision was made to offer Sub-T anesthesia due to intolerable pain from prior PRP treatments in all subjects. We observed all subjects were able to tolerate a significantly greater extent of PRP with Sub-T anesthesia even with presence of VH, oftentimes undergoing thousands of laser spots and capable to complete treatment in same clinic visit. By comparison, prior PRP treatments (without Sub-T anesthesia) were much less extensive sometimes involving only a few laser spots. We conclude that Sub-T anesthesia allows a tier of pain control for those not able to tolerate traditional PRP without anesthesia performed in the eye clinic. This new information suggests that certain patients undergoing PRP can be offered Sub-T anesthesia, and it will be important to define algorithm for selection of such individuals.