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1.  Modified mRNA as a new therapeutic option for pediatric respiratory diseases and hemoglobinopathies 
Background
The immunogenicity and limited stability of conventional messenger RNA (mRNA) has traditionally restricted its potential therapeutic use. In 1992, the first clinical application of mRNA was reported as a potential protein-replacement therapy; however, subsequent investigations have not been made for almost two decades. Recent developments, including increased stability, controlling immunogenicity, as well as utilization of mRNA encoding zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR-Cas9, have implicated modified mRNA as a very promising option for cancer immunotherapy, vaccines, protein expression replacement, and genome editing. This review aims to offer a summary of our present understanding of and improvements in mRNA-based drug technologies, along with a focus on the role in therapeutic options for pediatric respiratory diseases and hemoglobinopathies.
Conclusions
This mini review summarizes the recent advances in modified mRNA-based therapy and its potential therapeutic effect in treating major pediatric diseases.
doi:10.1186/s40348-015-0022-6
PMCID: PMC4654728  PMID: 26589812
Modified mRNA; Pediatric diseases; Gene therapy
2.  Association of Ficolin-2 Serum Levels and FCN2 Genetic Variants with Indian Visceral Leishmaniasis 
PLoS ONE  2015;10(5):e0125940.
Background
Visceral leishmaniasis (VL), one of the neglected tropical diseases, is endemic in the Indian subcontinent. Ficolins are circulating serum proteins of the lectin complement system and involved in innate immunity.
Methods
We have estimated ficolin-2 serum levels and analyzed the functional variants of the encoding gene FCN2 in 218 cases of VL and in 225 controls from an endemic region of India.
Results
Elevated levels of serum ficolin-2 were observed in VL cases compared to the controls (adjusted P<0.0001). The genetic analysis revealed that the FCN2 structural variant +6359 C>T (p.T236M) was associated with VL (OR=2.2, 95% CI=1.23-7.25, P=0.008) and with high ficolin-2 serum levels. We also found that the FCN2*AAAC haplotype occurred more frequently among healthy controls when compared to cases (OR=0.59, 95%CI=0.37-0.94, P=0.023).
Conclusions
Our findings indicate that the FCN2 variant +6359C>T is associated with the occurrence of VL and that ficolin-2 serum levels are elevated in Leishmania infections.
doi:10.1371/journal.pone.0125940
PMCID: PMC4428791  PMID: 25965808
3.  Lectin Complement Protein Collectin 11 (CL-K1) and Susceptibility to Urinary Schistosomiasis 
PLoS Neglected Tropical Diseases  2015;9(3):e0003647.
Background
Urinary Schistosomiasis is a neglected tropical disease endemic in many sub Saharan -African countries. Collectin Kidney 1 (CL-K1, encoded by COLEC11 on chromosome 2p25.3), a member of the vertebrate C-type lectin super family, has recently been identified as pattern-recognition molecule (PRR) of the lectin complement pathway. CL-K1 is preferentially expressed in the kidneys, but also in other organs and it is considered to play a role in host defense to some infectious agents. Schistosome teguments are fucosylated and CL-K1 has, through its collagen-like domain, a high binding affinity to fucose.
Methodology/Principal Findings
We utilized a Nigerian study group consisting of 167 Schistosoma haematobium infected individuals and 186 matched healthy subjects, and investigated the contribution of CL-K1 deficiency and of COLEC11 polymorphisms to infection phenotype. Higher CL-K1 serum levels were associated with decreased risk of schistosome infection (Pcorr = 0.0004). CL-K1 serum levels were differentially distributed between the COLEC11 genotypes and haplotypes observed. The non-synonymous variant p.R216H was associated with the occurrence of schistosomiasis (OR = 0.44, 95%CI = 0.22–0.72, Pcorr = 0.0004). The reconstructed COLEC11*TCCA haplotypes were associated with higher CL-K1 serum levels (P = 0.002) and with decreased schistosomiasis (OR = 0.38, 95%CI = 0.23–0.63, Pcorr = 0.0001).
Conclusions
In agreement with findings from our earlier published study, our findings support the observation that CL-K1 and their functional variants may be host factors associated with protection in schistosomiasis and may be a useful marker for further investigations.
Author Summary
Collectin Kidney 1 (CL-K1) was discovered in 2006. It is a pattern-recognition molecule (PRR) of the lectin complement pathway and is mainly expressed in the kidneys. We investigated a possible functional role of CL-K1 during urinary schistosomiasis on the basis of the rationale: i). Schistosome teguments are fucosylated and CL-K1 has high binding affinity to fucose ii). As CL-K1 is structurally similar to MBL, we hypothesize the involvement of CL-K1 in immune modulation during urinary schistosomiasis. We investigated the circulating CL-K1 serum levels in our study group. We initially screened the entire promoter and the exons of the COLEC11 gene for population specific variants. We validated four promoter variants and one non-synonymous substitution in exon8 for possible associations with urinary schistosomiasis and circulating CL-K1 serum levels. The study was conducted in Nigeria where the largest number of registered cases of schistosomiasis (29 million) for any sub-Saharan African country has been documented. Our findings support the observation that CL-K1 and functional variants are host factors that may be associated with protection in schistosomiasis and may be a useful marker for further investigations.
doi:10.1371/journal.pntd.0003647
PMCID: PMC4373859  PMID: 25807310
4.  IL-4 Haplotype -590T, -34T and Intron-3 VNTR R2 Is Associated with Reduced Malaria Risk among Ancestral Indian Tribal Populations 
PLoS ONE  2012;7(10):e48136.
Background
Interleukin 4 (IL-4) is an anti-inflammatory cytokine, which regulates balance between TH1 and TH2 immune response, immunoglobulin class switching and humoral immunity. Polymorphisms in this gene have been reported to affect the risk of infectious and autoimmune diseases.
Methods
We have analyzed three regulatory IL-4 polymorphisms; -590C>T, -34C>T and 70 bp intron-3 VNTR, in 4216 individuals; including: (1) 430 ethnically matched case-control groups (173 severe malaria, 101 mild malaria and 156 asymptomatic); (2) 3452 individuals from 76 linguistically and geographically distinct endogamous populations of India, and (3) 334 individuals with different ancestry from outside India (84 Brazilian, 104 Syrian, and 146 Vietnamese).
Results
The -590T, -34T and intron-3 VNTR R2 alleles were found to be associated with reduced malaria risk (P<0.001 for -590C>T and -34C>T, and P = 0.003 for VNTR). These three alleles were in strong LD (r2>0.75) and the TTR2 (-590T, -34T and intron-3 VNTR R2) haplotype appeared to be a susceptibility factor for malaria (P = 0.009, OR = 0.552, 95% CI = 0.356 –0.854). Allele and genotype frequencies differ significantly between caste, nomadic, tribe and ancestral tribal populations (ATP). The distribution of protective haplotype TTR2 was found to be significant (χ23 = 182.95, p-value <0.001), which is highest in ATP (40.5%); intermediate in tribes (33%); and lowest in caste (17.8%) and nomadic (21.6%).
Conclusions
Our study suggests that the IL-4 polymorphisms regulate host susceptibility to malaria and disease progression. TTR2 haplotype, which gives protection against malaria, is high among ATPs. Since they inhabited in isolation and mainly practice hunter-gatherer lifestyles and exposed to various parasites, IL-4 TTR2 haplotype might be under positive selection.
doi:10.1371/journal.pone.0048136
PMCID: PMC3480467  PMID: 23110190

Results 1-4 (4)