Hong-Liu Ding

307 Hospital of the Chinese People's Liberation Army, Peping, Beijing, China

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Publications (7)10.74 Total impact

  • Source
    Chang-Ming Geng, Hong-Liu Ding
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    ABSTRACT: RNA interference (RNAi) is a potential cure for amyotrophic lateral sclerosis (ALS) caused by dominant, gain-of-function superoxide dismutase 1 (SOD1) mutations. The success of such therapy relies on the functional small interfering RNAs (siRNAs) that can effectively deliver RNAi. This study aimed to design the functional siRNAs targeting ALS-associated mutant alleles. A modified dual luciferase system containing human SOD1 mRNA target was established to quantify siRNA efficacy. Coupled with validated siRNAs identified in the literature, we analyzed the rationale of siRNA design and subsequently developed an asymmetry rule-based strategy for designing siRNA. We then further tested the effectiveness of this design strategy in converting a naturally symmetric siRNA into functional siRNAs with favorable asymmetry for gene silencing of SOD1 alleles. The efficacies of siRNAs could vary tremendously by one base-pair position change. Functional siRNAs could target the whole span of SOD1 mRNA coding sequence as well as non-coding region. While there is no distinguishable pattern of the distribution of nucleobases in these validated siRNAs, the high percent of GC count at the last two positions of siRNAs (P18 and P19) indicated a strong effect of asymmetry rule. Introducing a mismatch at position 1 of the 5' of antisense strand of siRNA successfully converted the inactive siRNA into functional siRNAs that silence SOD1 with desired efficacy. Asymmetry rule-based strategy that incorporates a mismatch into siRNA most consistently enhances RNAi efficacy and guarantees producing functional siRNAs that successfully silence ALS-associated SOD1 mutant alleles regardless target positions. This strategy could also be useful to design siRNAs for silencing other disease-associated dominant, gain-of-function mutant genes.
    Chinese medical journal 01/2011; 124(1):106-10. · 0.90 Impact Factor
  • Xiao-Ping Wang, Bo-Min Sun, Hong-Liu Ding
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    ABSTRACT: To study procedural learning changes in patients with non-demented Parkinson disease (PD) but without depression. The Nissen serial reaction time task (SRTT) software version II (as a task of procedural learning), the Wechsler Memory Scale-Chinese version (WMS-CR), and two tasks of implicit memory were applied to 20 PD patients with a Hoehn-Yahr score at I-II degrees and 20 matched healthy controls were enrolled for the Nissen Version test. In the explicit WMS-CR and the implicit (word stem completion and degraded picture naming) tasks, the patients' scores fell within normal limits. In the SRTT, healthy controls displayed significantly reduced response times and error rates across the blocks of repeated sequence trials. In contrast, PD patients only showed a reduction in error rates but no change in response times. Impairment of nigrostriatal pathways selectively affects the performance in visuo-motor learning tasks such as the SRTT, but not in both the explicit tasks of WMS-CR and the implicit tasks.
    Neuroscience Letters 11/2008; 449(3):161-3. · 2.03 Impact Factor
  • Xiao-Ping Wang, Hong-Liu Ding
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    ABSTRACT: Alzheimer's disease (AD) is an increasing epidemic threatening public health. Both men and women are susceptible to the disease although women are at a slightly higher risk. The prevalence of AD rises exponentially in elderly people from 1% at age of 65 to approximately 40%-50% by the age of 95. While the cause of the disease has not been fully understood, genetics plays a role in the onset of the disease. Mutations in three genes (APP, PSEN1, and PSEN2) have been found to cause AD and APOE4 allele increases the risk of the disease. As human genomic research progresses, more genes have been identified and linked with AD. Genetic screening tests for persons at high risk of AD are currently available and may help them as well as their families better prepare for a later life with AD.
    Neuroscience Bulletin 05/2008; 24(2):105-9. · 1.37 Impact Factor
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    ABSTRACT: Migraine is a complex and heterogeneous disorder. Although several genetic models has been proposed including autosomal-dominant/autosomal recessive, sex-linked, sex-limited, mitochondrial, and multi-gene, none of these models can well-explain the transmission of the disease. We hypothesied that migraine is a sex-conditioned inherited disorder (autosomal dominant in females and autosomal recessive in males). This hypothesis is supported by the evidence such as the locations of genes associated with familial hemiplegic migraine, possibly "typical" migraine as well (dominantly on chromosome 19p, 1q, and 2q), male:female ratio of prevalence (1:2-1:4), the mostly youth-onset, the provocation by the contraceptives, the induction by menstruation, and the self-limitation after menopause. Female sex-hormones appear to be the key contributor to a higher prevalence of migraine in female. Socio-environmental factors may also play an important role.
    Neuroscience Bulletin 05/2008; 24(2):110-6. · 1.37 Impact Factor
  • Source
    Chang-ming Geng, Hong-liu Ding
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    ABSTRACT: Our previous study demonstrated an siRNA-mediated, allele-specific silencing of mutant genes that cause amyotrophic lateral sclerosis. To improve siRNA design for better therapeutic use of RNA interference, we systematically tested the base-pairing mismatch strategy in the design of asymmetric siRNA. A naturally symmetric siRNA that targets the human Cu Zn superoxide dismutase G85R mutant allele was modified by placing either 1 or 2 mismatches at the end of the siRNA from position 1 to 4 at each time. The target preference and silencing efficacy of modified siRNA were measured using a modified dual luciferase system. The modification of single base-pairing mismatch successfully achieved the conversion of the siRNA that was originally favored to the antisense of the mutant allele to the one that was favored to the sense strand of the gene. Compared to the single-mismatched siRNA, those with double-mismatch at one end demonstrated an increased asymmetry, and thus, an enhanced specificity and efficacy of gene silencing. In addition, the siRNA with double-mismatch at both ends remained in symmetry. Our results suggest the effectiveness of converting a symmetric siRNA to an asymmetric one by introducing mismatches into its structure, and the superiority of double-mismatched siRNA to single-mismatched siRNA in producing selective gene silencing resulting from the disruption of siRNA symmetry. The double-mismatch strategy is an improvement of the single-mismatch method and could be useful in the design of effective siRNAs for the treatment of diseases caused by dominant, gain-of-function gene mutations, such as ALS.
    Acta Pharmacologica Sinica 03/2008; 29(2):211-6. · 2.35 Impact Factor
  • Xiao-Ping Wang, Hong-Liu Ding
    Neuroscience Bulletin 01/2008; 24(2):105-109. · 1.37 Impact Factor
  • Neuroscience Bulletin 01/2008; 24(2):110-116. · 1.37 Impact Factor

Publication Stats

34 Citations
277 Views
10.74 Total Impact Points

Institutions

  • 2011
    • 307 Hospital of the Chinese People's Liberation Army
      Peping, Beijing, China
  • 2008
    • Shanghai Putuo District People's Hospital
      Shanghai, Shanghai Shi, China
    • University of Massachusetts Medical School
      • Meyers Primary Care Institute
      Worcester, Massachusetts, United States